Educational Forum with Clinical Studies Current Science and Research

BIBLIOGRAPHY

Easy to Read Books

1. Biology of Belief
2. How we live and why we die
3. Electron Gated Ion Channels

Scientific Experimental Studies on Signaling and Anti-aging
Spatiotemporal control of cell signalling using a light-switchable protein interaction

A Levskaya, OD Weiner, WA Lim, CA Voigt – Nature, 2009 – nature.com
An energy budget for signaling in the grey matter of the brain

D Attwell, SB Laughlin – Journal of Cerebral Blood Flow & Metabolism, 2001 – nature.com

… Assuming a much smaller ATP usage on G protein signaling, a total of approximately 3000 ATPs

will be … Control of endocytosis by clathrin, adaptor proteins, dynamin, and hsc70 also uses ATP. …

For signaling by active cells at 0.62 Hz, this optimum is broad, with 3 (of 10) or 4 (of 9
Minimal model for signal-induced Ca2+ oscillations and for their frequency encoding through protein phosphorylation.

A Goldbeter, G Dupont… – Proceedings of the …, 1990 – National Acad Sciences
Secreted form of β‐amyloid precursor protein shifts the frequency dependency for induction of LTD, and enhances LTP in hippocampal slices

A Ishida, K Furukawa, JN Keller, MP Mattson – Neuroreport, 1997 – journals.lww.com

… 15 Although a receptor for sAPPα has not yet been isolated, a signaling pathway that … The level

of cGMP in control slices was approximately 0.7 pmol/mg protein, and the … stimulation frequency

represents a crossover point between induction of LTD at lower frequencies and LTP
Complexity of calcium signaling in synaptic spines

KM Franks, TJ Sejnowski – Bioessays, 2002 – Wiley Online Library
Physiological signalling across cell membranes and cooperative influences of extremely low frequency electromagnetic fields

WR Adey – Biological coherence and response to external stimuli, 1988 – Springer

… As a further option, we have hypothesized that this transmembrane signalling may involve

nonlinear vibra- tion modes in helical proteins and generation of … lymphocytes exposed to a low

level RF field (450 MHz, 1.0 mW/cm2 ), cAMP-independent protein kinases showed
Impairments in high-frequency transmission, synaptic vesicle docking, and synaptic protein distribution in the hippocampus of BDNF knockout mice

LD Pozzo-Miller, W Gottschalk, L Zhang… – The Journal of …, 1999 – Soc Neuroscience
Complexity of calcium signaling in synaptic spines

KM Franks, TJ Sejnowski – Bioessays, 2002 – Wiley Online Library

… 19,61) protein phosphatase I,(20) calcineurin.(59,60) nNOS(62) and MAPK.(63) In addition to

signaling proteins, the PSD also contains scaffolding proteins. One such protein is PSD-95 (also

called SAP-90), first isolated by Kennedy and colleagues.(64) Although PSD-95
[HTML] Visual experience and deprivation bidirectionally modify the composition and function of NMDA receptors in visual cortex

BD Philpot, AK Sekhar, HZ Shouval, MF Bear – Neuron, 2001 – Elsevier

… First, biochemical experiments have shown, at the level of both mRNA and protein, that the

NR2A/B ratio increases in visual cortex … of the synaptic depression, and PL is the plateau potential,

or steady state, and K + PL = 1. At 40 Hz stimulation, a frequency where we
Minimal model for signal-induced Ca2+ oscillations and for their frequency encoding through protein phosphorylation.

A Goldbeter, G Dupont… – Proceedings of the …, 1990 – National Acad Sciences

… USA Vol. 87, pp. 1461-1465, February 1990 Biophysics Minimal model for signal-induced Ca2+

oscillationsand for their frequency encoding through protein phosphorylation (Ca2+

signaling/inositol 1,4,5-trisphosphate/biochemical oscillations/Ca2+-activated protein kinase)
[HTML] Visual experience and deprivation bidirectionally modify the composition and function of NMDA receptors in visual cortex

BD Philpot, AK Sekhar, HZ Shouval, MF Bear – Neuron, 2001 – Elsevier

… First, biochemical experiments have shown, at the level of both mRNA and protein, that the

NR2A/B ratio increases in visual cortex … of the synaptic depression, and PL is the plateau potential,

or steady state, and K + PL = 1. At 40 Hz stimulation, a frequency where we
Theories of biological aging: genes, proteins, and free radicals

SIS Rattan – Free radical research, 2006 – Taylor & Francis

… of these genes have well defined roles in normal metabolism, in intra- and inter-cellular signaling,

and in … such as methylated cytosines, oxidatively modified nucleotides, alternatively spliced RNAs,

and post-translationally modified proteins, including protein folding
Amino acid signalling and the integration of metabolism

AJ Meijer, PF Dubbelhuis – Biochemical and biophysical research …, 2004 – Elsevier
[HTML] Peroxisome metabolism and cellular aging

VI Titorenko, SR Terlecky – Traffic, 2011 – Wiley Online Library
RETRACTED: Expression of the longevity proteins by both red and white wines and their cardioprotective components, resveratrol, tyrosol, and hydroxytyrosol

S Mukherjee, I Lekli, N Gurusamy, AAA Bertelli… – Free Radical Biology …, 2009 – Elsevier
Regulation of oxidative stress by the anti–aging hormone klotho

M Yamamoto, JD Clark, JV Pastor, P Gurnani… – Journal of Biological …, 2005 – ASBMB
Suppression of aging by the hormone Klotho

H Kurosu, M Yamamoto, JD Clark, JV Pastor, A Nandi… – Science, 2005 – sciencemag.org
Dynamic regulation of RGS2 suggests a novel mechanism in G-protein signaling and neuronal plasticity

T Ingi, AM Krumins, P Chidiac… – The Journal of …, 1998 – Soc Neuroscience
[HTML] Frequency selectivity, multistability, and oscillations emerge from models of genetic regulatory systems

P Smolen, DA Baxter, JH Byrne – American Journal of …, 1998 – Am Physiological Soc

… been characterized, it has become increasingly evident that nonlinear interactions, positive and

negative feedback within signaling pathways, time … A second well-known group of TFs is the

activating protein-1 (AP-1) family of heterodimers of Fos and Jun proteins, which bind …

Cited by 145 Related articles All 7 versions Cite Save

[HTML] from jneurosci.org

Long-term potentiation induced by θ frequency stimulation is regulated by a protein phosphatase-1-operated gate

GP Brown, RD Blitzer, JH Connor… – The Journal of …, 2000 – Soc Neuroscience

… long-term potentiation (LTP) is induced when stimulation is delivered at higher frequencies

(30–100 Hz … is sensitive to certain pharmacological manipulations, including the inhibition of protein

kinases or … agonist, an effect that is mediated by the cAMP-signaling pathway (Thomas …

Cited by 79 Related articles All 6 versions Cite Save

[HTML] from sciencedirect.com

[HTML] Rap1 couples cAMP signaling to a distinct pool of p42/44MAPK regulating excitability, synaptic plasticity, learning, and memory

A Morozov, IA Muzzio, R Bourtchouladze, N Van-Strien… – Neuron, 2003 – Elsevier

… of GTP bound Ras precipitated from whole hippocampal extract (15 or 50 μg of protein). … Most

of these induction protocols involve theta frequencies (5–12 Hz), which are present in the … LTP,

a cAMP-dependent protocol (Winder et al., 1999), may recruit signaling cascades similar …

Cited by 213 Related articles All 8 versions Cite Save

[PDF] from researchgate.net

Nitric oxide signaling in the central nervous system

J Garthwaite, CL Boulton – Annual review of physiology, 1995 – annualreviews.org

… The results also support the hypothesis (50) that, so far as interneuronal signaling is concerned,

NO … In its phosphorylated form, DARPP-32 is a potent inhibitor of protein phosphatase 1; hence,

through this mechanism, NO could maintain enzyme or receptor proteins in their …

Cited by 1579 Related articles All 9 versions Cite Save

Energy dissipation kinetics for protein and antibody-antigen adsorption under shear oscillation on a quartz crystal microbalance

F Höök, M Rodahl, P Brzezinski, B Kasemo – Langmuir, 1998 – ACS Publications

… For Fer the initial slope is considerably higher than the asymptotic one, signaling more dissipation

per added molecule … b of Figures 2. We suggest, tentatively, that these observations indicate

structural alterations within the individual proteins or within the protein layer as …

Cited by 499 Related articles All 4 versions Cite Save

Effects of extremely low frequency (50 Hz) magnetic field on morphological and biochemical properties of human keratinocytes

V Manni, A Lisi, D Pozzi, S Rieti, A Serafino… – …, 2002 – Wiley Online Library

… Glutamate-induced protein phosphorylation in cerebellar granule cells: Role of protein kinase

1. Neurochem Res 19(10):1257 … Role of Smad proteins and transcrip- … Signaling from E-cadherins

to the MAPK pathway by the recruitment and activation of epidermal growth factor …

Cited by 71 Related articles All 6 versions Cite Save

Review article: cyclic AMP sensors in living cells: what signals can they actually measure?

TC Rich, JW Karpen – Annals of biomedical engineering, 2002 – Springer

… cAMP.69,70 Increased cAMP lev- els activate effector proteins, including protein kinase A … Both

of the sensors uti- lize heterologously expressed effector proteins to mea- sure cAMP. … Ca2

signaling pathways, there is reason to believe that cAMP signals are also dynamic.14,58
Regulation of fibroblast growth factor-23 signaling by klotho

H Kurosu, Y Ogawa, M Miyoshi, M Yamamoto… – Journal of Biological …, 2006 – ASBMB
Loss of Kv3. 1 tonotopicity and alterations in cAMP response element-binding protein signaling in central auditory neurons of hearing impaired mice

CAA von Hehn, A Bhattacharjee… – The Journal of …, 2004 – Soc Neuroscience
… -dependent regulation of gene expression: temporal specificity in Ca2+, cAMP-responsive element binding proteins, and mitogen-activated protein kinase signaling

RD Fields, F Eshete, B Stevens… – The Journal of …, 1997 – Soc Neuroscience
Identification and characterization of proteins interacting with SIRT1 and SIRT3: implications in the anti‐aging and metabolic effects of sirtuins

IKM Law, L Liu, A Xu, KSL Lam, PM Vanhoutte… – …, 2009 – Wiley Online Library
SynGAP regulates ERK/MAPK signaling, synaptic plasticity, and learning in the complex with postsynaptic density 95 and NMDA receptor

NH Komiyama, AM Watabe, HJ Carlisle… – The Journal of …, 2002 – Soc Neuroscience

… suggesting that PSD-95 may couple NMDA receptors to multiple downstream signaling pathways

with very … morphological synapses, as shown by immunostaining with the synaptic vesicle proteins

synaptophysin and … c, MAP2; immunohistochemistry for dendritic marker protein. …

[HTML] Impaired electrical signaling disrupts gamma frequency oscillations in connexin 36-deficient mice

SG Hormuzdi, I Pais, FEN LeBeau, SK Towers… – Neuron, 2001 – Elsevier

… demonstrate that the deletion of Cx36, a major neuronal gap junction protein, leads to … Within the

mutually connected interneuronal network, such an impairment of electrical signaling is likely …

However, the majority of activity at γ frequencies is recorded from the hippocampus in …
Regulator of G-protein signaling protein 2 modulates purinergic calcium and ciliary beat frequency responses in airway epithelia

MC Nlend, RJ Bookman, GE Conner… – American journal of …, 2002 – Am Thoracic Soc

… Among the known RGS proteins, RGS2, RGS3, and RGS4 bind to and inhibit Gαq-mediated … RGS2

represents one of the points of regulation of P2Y-receptor signaling in mammalian … The plasmid

encoding an EGFP-RGS2 fusion protein (based on pEGFP-N3 from Clontech) was …
[HTML] Autophagy and aging

DC Rubinsztein, G Mariño, G Kroemer – Cell, 2011 – Elsevier
Growth hormone receptor deficiency is associated with a major reduction in pro-aging signaling, cancer, and diabetes in humans

J Guevara-Aguirre, P Balasubramanian… – Science translational …, 2011 – stm.sciencemag.org
Neuronal plasticity: increasing the gain in pain

CJ Woolf, MW Salter – Science, 2000 – sciencemag.org

… modulation is phosphorylation of receptor/ion channels, or associated regulatory proteins, altering

intrinsic … membrane-bound receptors (17) activating protein kinase A (18) or protein kinase C ɛ …

At CA1 synapses, LTP is initiated by a signaling cascade involving enhancement of …
AMP-activated protein kinase signaling activation by resveratrol modulates amyloid-β peptide metabolism

V Vingtdeux, L Giliberto, H Zhao, P Chandakkar… – Journal of Biological …, 2010 – ASBMB
Neuroprotective effects of anti–aging oriental medicine Lycium barbarum against β-amyloid peptide neurotoxicity

MS Yu, SKY Leung, SW Lai, CM Che, SY Zee… – Experimental …, 2005 – Elsevier
[HTML] AMP-activated protein kinase (AMPK) controls the aging process via an integrated signaling network

A Salminen, K Kaarniranta – Ageing research reviews, 2012 – Elsevier
[PDF] Potential anti–aging agents suppress the level of constitutive mTOR-and DNA damage-signaling

HD Halicka, H Zhao, J Li, YS Lee, TC Hsieh… – Aging (Albany …, 2012 – impactaging.com
Sirtuin regulation of mitochondria: energy production, apoptosis, and signaling

E Verdin, MD Hirschey, LWS Finley… – Trends in biochemical …, 2010 – Elsevier
Signalling and autophagy regulation in health, aging and disease

AJ Meijer, P Codogno – Molecular aspects of medicine, 2006 – Elsevier
Activation of innate immunity system during aging: NF-kB signaling is the molecular culprit of inflamm-aging

A Salminen, J Huuskonen, J Ojala, A Kauppinen… – Ageing research …, 2008 – Elsevier
[PDF] Research The anti–aging gene KLOTHO is a novel target for epigenetic silencing in human cervical carcinoma

J Lee, DJ Jeong, J Kim, S Lee, JH Park, B Chang… – 2010 – biomedcentral.com
Molecular chaperones as regulatory elements of cellular networks

C Sőti, C Pál, B Papp, P Csermely – Current opinion in cell biology, 2005 – Elsevier
Aging cellular networks: chaperones as major participants

C Sőti, P Csermely – Experimental gerontology, 2007 – Elsevier
[HTML] The choice between p53-induced senescence and quiescence is determined in part by the mTOR pathway

LG Korotchkina, OV Leontieva, EI Bukreeva… – Aging (Albany …, 2010 – ncbi.nlm.nih.gov
Inflamm‐aging: an evolutionary perspective on immunosenescence

C Franceschi, M Bonafè, S Valensin… – Annals of the New …, 2000 – Wiley Online Library
Signaling pathways in mitochondrial dysfunction and aging

C Mammucari, R Rizzuto – Mechanisms of ageing and development, 2010 – Elsevier
Impaired p38 MAPK/HSP27 signaling underlies aging-related failure in opioid-mediated cardioprotection

JN Peart, ER Gross, JP Headrick, GJ Gross – Journal of molecular and …, 2007 – Elsevier
PGC-1α in aging and anti–aging interventions

R Anderson, T Prolla – Biochimica et Biophysica Acta (BBA)-General …, 2009 – Elsevier
Aging, anti–aging, and hormesis

SIS Rattan – Mechanisms of ageing and development, 2004 – Elsevier
K6PC-5, a sphingosine kinase activator, induces anti–aging effects in intrinsically aged skin through intracellular Ca 2+ signaling

JK Youm, H Jo, JH Hong, DM Shin, MJ Kwon… – Journal of …, 2008 – Elsevier
Antagonizing β-amyloid peptide neurotoxicity of the anti–aging fungus Ganoderma lucidum

CSW Lai, MS Yu, WH Yuen, KF So, SY Zee… – Brain research, 2008 – Elsevier

… Synaptophysin is one of the most abundant pre-synaptic vesicle proteins (Phelan and Gordon …

1. lucidum attenuated Aβ-induced synaptotoxicity by preserving a synaptic density protein,

synaptophysin, in … A recent report shows that the stress signaling pathway of JNK
Effects of the Pit1 mutation on the insulin signaling pathway: implications on the longevity of the long-lived

CC Hsieh, JH DeFord, K Flurkey, DE Harrison… – Mechanisms of ageing …, 2002 – Elsevier
Growth hormone-induced alterations in the insulin-signaling system

FP Dominici, D Turyn – Experimental biology and medicine, 2002 – ebm.sagepub.comAutophagy and aging: keeping that old broom working

AM Cuervo – Trends in Genetics, 2008 – Elsevier
[HTML] … Dimethylarginine System Role of Angiotensin II Type 1 Receptor and Peroxisome Proliferator Activated Receptor γ Signaling During Endothelial Aging

F Scalera, J Martens-Lobenhoffer, A Bukowska… – …, 2008 – Am Heart Assoc
[HTML] Inflammation and endothelial dysfunction during aging: role of NF-κB

A Csiszar, M Wang, EG Lakatta… – Journal of Applied …, 2008 – Am Physiological Soc
Mitochondria and the autophagy–inflammation–cell death axis in organismal aging

DR Green, L Galluzzi, G Kroemer – Science, 2011 – sciencemag.org
[HTML] How to live long and prosper: autophagy, mitochondria, and aging

WL Yen, DJ Klionsky – Physiology, 2008 – Am Physiological Soc
Anti-apoptotic and anti-senescence effects of Klotho on vascular endothelial cells

M Ikushima, H Rakugi, K Ishikawa, Y Maekawa… – Biochemical and …, 2006 – Elsevier
Interaction of aging-associated signaling cascades: inhibition of NF-κB signaling by longevity factors FoxOs and SIRT1 A Salminen, J Ojala, J Huuskonen… – Cellular And Molecular …, 2008 – Springer

[HTML] RAGE signaling in inflammation and arterial aging

L Lin, S Park, EG Lakatta – Frontiers in bioscience: a journal and …, 2009 – ncbi.nlm.nih.gov

Protein kinase A signaling as an anti–aging target

LC Enns, W Ladiges – Ageing research reviews, 2010 – Elsevier
[HTML] Age-related differences in skeletal muscle insulin signaling: the role of stress kinases and heat shock proteins

AA Gupte, GL Bomhoff… – Journal of Applied …, 2008 – Am Physiological Soc
The signaling hubs at the crossroad of longevity and age-related disease networks

M Wolfson, A Budovsky, R Tacutu, V Fraifeld – The international journal of …, 2009 – Elsevier
NF-κB signaling in the aging process

A Salminen, K Kaarniranta – Journal of clinical immunology, 2009 – Springer
Autophagy in cardiac myocyte homeostasis, aging, and pathology

A Terman, UT Brunk – Cardiovascular Research, 2005 – cardiovascres.oxfordjournals.org
HMG-CoA reductase inhibitors up-regulate anti–aging klotho mRNA via RhoA inactivation in IMCD3 cells

H Narumiya, S Sasaki… – Cardiovascular …, 2004 – cardiovascres.oxfordjournals.org
Extending healthy life span—from yeast to humans

L Fontana, L Partridge, VD Longo – science, 2010 – sciencemag.org
Insulin/IGF-1 and ROS signaling pathway cross-talk in aging and longevity determination

J Papaconstantinou – Molecular and cellular endocrinology, 2009 – Elsevier
The molecular inflammatory process in aging

HY Chung, B Sung, KJ Jung, Y Zou… – … & redox signaling, 2006 – online.liebertpub.com
Regulation of the aging process by autophagy

A Salminen, K Kaarniranta – Trends in molecular medicine, 2009 – Elsevier

… least three changes: (i) enhanced growth factor signaling; (ii) increased NF-κB signaling, which

activates … Bcl-2 and Bcl-x L ; and (iii) dysfunction of tumor suppressor proteins, such as … They also

demonstrated that only cytoplasmic p53 protein, but not nuclear p53, was capable of this process
Increased muscle PGC-1α expression protects from sarcopenia and metabolic disease during aging

T Wenz, SG Rossi, RL Rotundo… – Proceedings of the …, 2009 – National Acad Sciences
Exercise training attenuates age-induced changes in apoptotic signaling in rat skeletal muscle

W Song, HB Kwak, JM Lawler – Antioxidants & redox signaling, 2006 – online.liebertpub.com
Epigenetic oxidative redox shift (EORS) theory of aging unifies the free radical and insulin signaling theories

GJ Brewer – Experimental gerontology, 2010 – Elsevier
The regulation of aging: does autophagy underlie longevity?

T Vellai, K Takács-Vellai, M Sass, DJ Klionsky – Trends in cell biology, 2009 – Elsevier
Significance of protein tyrosine kinase/protein tyrosine phosphatase balance in the regulation of NF-κB signaling in the inflammatory process and aging

KJ Jung, EK Lee, BP Yu, HY Chung – Free Radical Biology and Medicine, 2009 – Elsevier
Pleiotropic effects of growth hormone signaling in aging

A Bartke – Trends in Endocrinology & Metabolism, 2011 – Elsevier
Overexpression of human thioredoxin controls oxidative stress and life span

A Mitsui, J Hamuro, H Nakamura… – … Redox Signaling, 2002 – online.liebertpub.com
Selective mitochondrial autophagy, or mitophagy, as a targeted defense against oxidative stress, mitochondrial dysfunction, and aging

JJ Lemasters – Rejuvenation research, 2005 – online.liebertpub.com
The free radical theory of aging

D Harman – Antioxidants and Redox Signaling, 2003 – online.liebertpub.com
Protein stress and stress proteins: implications in aging and disease

C Sőti, P Csermely – Journal of biosciences, 2007 – Springer
[HTML] The regulation of INK4/ARF in cancer and aging

WY Kim, NE Sharpless – Cell, 2006 – Elsevier

… In human cancers, the goal of defining which protein(s) at the locus represent the … and repression

of p15 INK4b has been noted in response to a few signaling events, such as … Some proteins

specifically influence the expression of a single locus member whereas others influence …
[HTML] Protein kinase A is a target for aging and the aging heart

LC Enns, C Pettan-Brewer, W Ladiges – Aging (Albany NY), 2010 – ncbi.nlm.nih.gov
Rejuvenation of the aging thymus: growth hormone-mediated and ghrelin-mediated signaling pathways

DD Taub, WJ Murphy, DL Longo – Current opinion in pharmacology, 2010 – Elsevier
The role of COX-2 and Nrf2/ARE in anti-inflammation and antioxidative stress: Aging and anti–aging

C Luo, E Urgard, T Vooder, A Metspalu – Medical hypotheses, 2011 – Elsevier
[HTML] Cell cycle arrest is not yet senescence, which is not just cell cycle arrest: terminology for TOR-driven aging

MV Blagosklonny – Aging (Albany NY), 2012 – ncbi.nlm.nih.gov
[CITATION] Insulin/IGF-like signalling, the central nervous system and aging

S Broughton, L Partridge – Biochem. J, 2009

Cited by 153 Related articles All 13 versions Cite Save
Characterization of aging-associated up-regulation of constitutive nuclear factor-κB binding activity

M Helenius, S Kyrylenko… – … and Redox Signaling, 2001 – online.liebertpub.com

… 30. Walter R, and Sierra F. Changes in hepatic DNA bind- ing proteins as a function of age in

rats. … HTLV-1 Tax protein binds to MEKK1 to stimulate IkB kinase activity and NF-kB activation. …

2014. Noncoding RNAs regulate NF-κB signaling to modulate blood vessel inflammation. …
      Insulin/IGF signalling and ageing: seeing the bigger picture

D Gems, L Partridge – Current opinion in genetics & development, 2001 – Elsevier

… New insulin-like proteins with atypical disulfide bond pattern characterized in Caenorhabditis

elegans by comparative sequence analysis and homology modeling. … Food and metabolic

signalling defects in a Caenorhabditis elegans serotonin-synthesis mutant. …
Insulin signaling, GSK-3, heat shock proteins and the natural history of type 2 diabetes mellitus: a hypothesis

PL Hooper – Metabolic syndrome and related disorders, 2007 – online.liebertpub.com
Regulator of G-protein signaling-2 mediates vascular smooth muscle relaxation and blood pressure

M Tang, G Wang, P Lu, RH Karas, M Aronovitz… – Nature medicine, 2003 – nature.com
Induction of cAMP-dependent protein kinase A activity in human skin fibroblasts and rat osteoblasts by extremely low-frequency electromagnetic fields

S Thumm, M Löschinger, S Glock, H Hämmerle… – Radiation and …, 1999 – Springer
Temporal integration of intracellular Ca 2+ signaling networks in regulating gene expression by action potentials

RD Fields, PR Lee, JE Cohen – Cell calcium, 2005 – Elsevier

[HTML] Activity-dependent β-adrenergic modulation of low frequency stimulation induced LTP in the hippocampal CA1 region

MJ Thomas, TD Moody, M Makhinson, TJ O’Dell – Neuron, 1996 – Elsevier

… repetitive activation of excitatory synapses in the CA1 region of the hippocampus at 5 Hz is

sufficient to activate the protein kinase–dependent signaling cascade responsible for LTP, our

results suggest that prolonged periods of synaptic activity at this frequency will also activate
[HTML] Requirement of protein synthesis for group I mGluR-mediated induction of epileptiform discharges

LR Merlin, PJ Bergold… – Journal of …, 1998 – Am Physiological Soc

… mediating the burst prolongation (as opposed to that increasing the burst frequency), it appears

to … polypeptides by 96 ± 4%, and 30–60 μM cycloheximide inhibits total protein synthesis by … If basal

proteins present could serve as a substrate to support epileptogenesis, one would
[PDF] Biological effects of electromagnetic fields

WR Adey – Journal of cellular biochemistry, 1993 – energycelltherapy.co.uk

… INWARD SIGNALING ALONG CELL MEMBRANE RECEPTOR PROTEINS … intracellular loops

2 and 3. These are known sites of interaction of G proteins in rhodopsin … Adey I’fR 11984):

Alterations in protein kinase activity following exposure of cultured lymphocytes to modulated
Inactivation of calcium-binding protein genes induces 160 Hz oscillations in the cerebellar cortex

G Cheron, D Gall, L Servais, B Dan… – The Journal of …, 2004 – Soc Neuroscience
The role of elevations in intracellular [Ca2+] in the development of low frequency fatigue in mouse single muscle fibres.

ER Chin, DG Allen – The Journal of physiology, 1996 – Wiley Online Library

… due to decreased Ca2+ sensitivity or to decreases in maximum force- generating capacity of

the contractile proteins and therefore … much more prominent at low frequencies of stimulation

(30 or 50 Hz) than at high frequencies (100 Hz) and they called it low frequency fatigue.
Frequency-encoding Thr17 phospholamban phosphorylation is independent of Ser16 phosphorylation in cardiac myocytes

D Hagemann, M Kuschel, T Kuramochi, W Zhu… – Journal of Biological …, 2000 – ASBMB
Mechanical regulation of signaling pathways in bone

WR Thompson, CT Rubin, J Rubin – Gene, 2012 – Elsevier
[HTML] Frequency modulation of Ca2+ sparks is involved in regulation of arterial diameter by cyclic nucleotides

VA Porter, AD Bonev, HJ Knot… – American Journal of …, 1998 – Am Physiological Soc

… arteries.A: forskolin (10 μM) increases Ca 2+ spark frequency, and an inhibitor of protein kinase

A … C: time course of STOC frequency from experiment inA, plotted in 20-s bins. Mean STOC

amplitude and frequencies in this experiment were 25.4 pA and 2.08 Hz (control), 36.5 pA
Frequency-specific and D2 receptor-mediated inhibition of glutamate release by retrograde endocannabinoid signaling

HH Yin, DM Lovinger – … of the National Academy of Sciences, 2006 – National Acad Sciences
Example of Abstract on Signaling Frequences of Proteins

Frequency-specific and D2 receptor-mediated inhibition of glutamate release by retrograde endocannabinoid signaling

• Henry H. Yin and David M. Lovinger *

Author Affiliations

• Edited by Roger A. Nicoll, University of California, San Francisco, CA, and approved April 10, 2006 (received for review December 14, 2005)
• Abstract
• Full Text
• Authors & Info
• Figures
• Metrics
• Related Content
• PDF

 

Abstract

The mechanisms underlying modulation of corticostriatal synaptic transmission by D2-like receptors (D2Rs) have been controversial. A recent study suggested that D2Rs inhibit glutamate release at this synapse, but only during high-frequency synaptic activation. Because the release of postsynaptic endocannabinoids (eCBs), which act as retrograde messengers to inhibit presynaptic glutamate release, can be triggered by D2R activation and intense synaptic activation, such a mechanism could mediate dopaminergic modulation of corticostriatal transmission. Here, we show that D2R activation reduces excitatory transmission onto striatal medium spiny neurons at a stimulation frequency of 20 Hz but not at 1 Hz. This form of inhibition requires CB1 receptor activation, as evidenced by the fact that it is blocked by AM251 [N-(piperidin-1-yl)-1-(2,4-dichlorophenyl)-5-(4-chlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide], a CB1 antagonist, and is absent in CB1 knockout mice. It is also blocked by postsynaptic intracellular calcium chelation, by group I metabotropic glutamate receptor antagonism, and by inhibition of postsynaptic phospholipase C. These results demonstrate a previously unrecognized role for retrograde eCB signaling in reversible and frequency-specific inhibition of glutamate release by the activation of striatal D2Rs.

[HTML] Selective regulation of cellular processes via protein cascades acting as band-pass filters for time-limited oscillations

M Marhl, M Perc, S Schuster – FEBS letters, 2005 – Elsevier

… Bow-tie signalling scheme for selective regulation of cellular processes by Ca 2+ oscillations. …

curves has two maxima corresponding to the two frequencies of oscillations at which the proteins

are most … ν = 0.05 Hz and ν = 1.2 Hz, (B) activation of the third-level protein in process
Selective regulation of cellular processes via protein cascades acting as band-pass filters for time-limited oscillations

Edited by Robert B. Russell

• Marko Marhl^{a, ,} , Matjaž Perc^a, Stefan Schuster^b

VALIDHTMLVALIDHTMLVALIDHTML

 

VALIDHTML

Under an Elsevier user license

Show more

VALIDHTML

doi:10.1016/j.febslet.2005.09.007

Get rights and content

 

Referred To By

FRAGMENTEND

 

VALIDHTML

Open Archive

 

Abstract

We show by mathematical modelling that a two-level protein cascade can act as a band-pass filter for time-limited oscillations. The band-pass filters are then combined into a network of three-level signalling cascades that by filtering the frequency of time-limited oscillations selectively switches cellular processes on and off. The physiological relevance for the selective regulation of cellular processes is demonstrated for the case of regulation by time-limited calcium oscillations.

VALIDHTML

 

VALIDHTML

Keywords

• Band-pass filter; Signalling cascade; Bow-tie structure; Calcium oscillations

VALIDHTML

 

1. Introduction

Band-pass filters are well known as electrical frequency filters. Also chemical reaction networks can act as band-pass filters [1] and [2]. All these filters were designed for sustained, theoretically infinitely long, oscillatory signals. In contrast to previous studies, we present a band-pass filter for time-limited oscillations. It is based on an enzyme cascade [3] and [4] in which each activated enzyme catalyses the activation of the protein on the next level.

VALIDHTML

We then combine the band-pass filters into a network that enables selective regulation of cellular processes. The striking feature of the network is that several inputs can influence several targets via only one or a few intermediary components. This architecture has been termed “bow-tie” or “hour-glass” structure [5] and [6] and characterises also several technical systems, for example, power grids or manufacturing [5]. In communication systems this architecture corresponds to multiplexers. Examples of such procedures are code-division multiple access (CDMA) and time-division multiplexing (TDMA) used by the GSM telephone system [7], for example.

VALIDHTML

The effectiveness of here proposed bow-tie architecture for selective regulation of cellular processes is demonstrated for the case of regulation by time-limited Ca²⁺ oscillations. This seems to be of special physiological importance since Ca²⁺ oscillations play an important role in intra- and intercellular signal transduction by regulating many cellular processes, from egg fertilisation to cell death [8], [9] and [10]. There exists experimental evidence that the duration of Ca²⁺ signals modulates gene transcription [11] and egg fertilisation [12], for example. For plant cells, it has been shown that the duration and number of Ca²⁺ spikes regulate the aperture of stomatal pores [13] and [14]. Therefore, we use time-limited Ca²⁺ oscillations for studying the selective regulation of cellular processes. The Ca²⁺ oscillations are simulated by artificially generated square-shaped signals as also used in some experiments [15] and theoretical studies [16] and [17].

VALIDHTML

2. Mathematical model

The regulation of cellular processes is modelled by a bow-tie signalling architecture (Fig. 1). Input stimuli evoke Ca²⁺ oscillations which regulate cellular processes via the network of signalling cascades. Our analysis includes kinase-phosphatase cascades that are organised as parallel branches in three levels. The third level is the activation level, and correspondingly, the whole branch containing one of the third-level proteins at the end is called the activation branch. Each activation branch can consist of several primary branches made up of first and second-level kinase-phosphatase cascades. In Fig. 1 two activation branches are presented in detail, each of them consisting of two primary branches.

VALIDHTML

<img class=”figure large” border=”0″ alt=”Bow-tie signalling scheme for selective regulation of cellular processes by Ca2+ …” src=”http://origin-ars.els-cdn.com/content/image/1-s2.0-S001457930501094X-gr1.gif” data-thumbEID=”1-s2.0-S001457930501094X-gr1.sml” data-imgEIDs=”1-s2.0-S001457930501094X-gr1.gif” data-fullEID=”1-s2.0-S001457930501094X-gr1.gif”>

Fig. 1.

Bow-tie signalling scheme for selective regulation of cellular processes by Ca²⁺ oscillations. The network of kinase-phosphatase cascades consists of activated (z_ij) and inactivated <img height=”18″ border=”0″ style=”vertical-align:bottom” width=”26″ alt=”View the MathML source” title=”View the MathML source” src=”http://origin-ars.els-cdn.com/content/image/1-s2.0-S001457930501094X-si1.gif”>(z˜ij)mathContainerLoading Mathjax proteins, where indices i ∈ [1, … ,n] and j ∈ [1,2] denote the primary branch number and the cascade level, respectively. For the third level of proteins, Roman indices indicate the number of the activation branch. Parameters <img height=”22″ border=”0″ style=”vertical-align:bottom” width=”72″ alt=”View the MathML source” title=”View the MathML source” src=”http://origin-ars.els-cdn.com/content/image/1-s2.0-S001457930501094X-si2.gif”>kij+

 

and

 

kij-mathContainerLoading Mathjax are the primary branch rate constants for the kinase and phosphatase reactions, respectively. <img height=”21″ border=”0″ style=”vertical-align:bottom” width=”76″ alt=”View the MathML source” title=”View the MathML source” src=”http://origin-ars.els-cdn.com/content/image/1-s2.0-S001457930501094X-si3.gif”>kAp+

 

and

 

kA-mathContainerLoading Mathjax denote the rate constants for each third-level protein, where A ∈ [I,II, … ,N] indicates the number of the activation branch, and p indicates the number of the primary (input) branch (see Eq. (4)). Note that primary branches may partly overlap (see text).

caption

Figure options

 

VALIDHTML

 

Time-limited Ca²⁺ oscillations are mimicked by square-shaped signals:

equation

(1)

<img height=”41″ border=”0″ style=”vertical-align:bottom” width=”368″ alt=”View the MathML source” title=”View the MathML source” src=”http://origin-ars.els-cdn.com/content/image/1-s2.0-S001457930501094X-si4.gif”>x(t)=

xmax	if((tmodg)⩾(g-d)and(t<Mg)),
xmin	else,

mathContainer

Turn

MathJax

on

Loading Mathjax

Comment

where x_min and x_max are the minimum and maximum of the oscillations, respectively, g denotes the period of oscillations, d is the spike width, and M is the number of Ca²⁺ spikes. In all calculations, we set d = 0.01s and M = 5.

 

VALIDHTML

For the ith primary branch (i ∈ [1, … ,n]), the concentrations of activated proteins at the first (z_i1) and second (z_i2) levels can be modelled as:

equation

(2)

<img height=”35″ border=”0″ style=”vertical-align:bottom” width=”200″ alt=”View the MathML source” title=”View the MathML source” src=”http://origin-ars.els-cdn.com/content/image/1-s2.0-S001457930501094X-si5.gif”>dzi

1

dt=ki

1

+(zi

1

tot-zi

1

)x

4

-ki

1

-zi

1

,

mathContainer

Turn

MathJax

on

Loading Mathjax

Comment

equation

(3)

<img height=”35″ border=”0″ style=”vertical-align:bottom” width=”202″ alt=”View the MathML source” title=”View the MathML source” src=”http://origin-ars.els-cdn.com/content/image/1-s2.0-S001457930501094X-si6.gif”>dzi

2

dt=ki

2

+(zi

2

tot-zi

2

)zi

1

4

-ki

2

-zi

2

,

mathContainer

Turn

MathJax

on

Loading Mathjax

Comment

respectively. We assume cooperativity in that four active molecules of the previous level must bind to activate a protein. Moreover, in Eqs. (2) and (3) the conservation relation for each protein cycle has been considered.

 

VALIDHTML

At the third level of the cascade network, the proteins are activated by one or several activated complexes from the second level. In general, the third level of the Ath activation branch (A ∈ [I,II, … ,N]) can be described as

equation

(4)

<img height=”35″ border=”0″ style=”vertical-align:bottom” width=”361″ alt=”View the MathML source” title=”View the MathML source” src=”http://origin-ars.els-cdn.com/content/image/1-s2.0-S001457930501094X-si7.gif”>dzAdt=kAp+(zAtot-zA)zp

2

4

+⋯+kAr+(zAtot-zA)zr

2

4

-kA-zA

,

mathContainer

Turn

MathJax

on

Loading Mathjax

Comment

where p, … ,r ∈ [1, … ,n] denote primary branches pertaining to the second level complexes by which the third-level protein of activation branch A is activated. In Section 3, we demonstrate the effectiveness of this architecture on a very simple network consisting of only two activation branches:

equation

(5)

<img height=”35″ border=”0″ style=”vertical-align:bottom” width=”310″ alt=”View the MathML source” title=”View the MathML source” src=”http://origin-ars.els-cdn.com/content/image/1-s2.0-S001457930501094X-si8.gif”>dzIdt=kI

1

+(zItot-zI)z

12

4

+kI

2

+(zItot-zI)z

22

4

-kI-zI

,

mathContainer

Turn

MathJax

on

Loading Mathjax

Comment

equation

(6)

<img height=”35″ border=”0″ style=”vertical-align:bottom” width=”333″ alt=”View the MathML source” title=”View the MathML source” src=”http://origin-ars.els-cdn.com/content/image/1-s2.0-S001457930501094X-si9.gif”>dzIIdt=kII

2

+(zIItot-zII)z

22

4

+kII

3

+(zIItot-zII)z

32

4

-kII-zII

.

mathContainer

Turn

MathJax

on

Loading Mathjax

Comment

The parameter values used throughout are listed in Table 1.

 

VALIDHTML

 

Table 1.

Parameter values

<img height=”393″ border=”0″ style=”vertical-align:bottom” width=”444″ alt=”Full-size image (42 K)” title=”Full-size image (42 K)” src=”http://origin-ars.els-cdn.com/content/image/1-s2.0-S001457930501094X-fx1.jpg”>

Table options

 

VALIDHTML

3. Results

For the cascade network (Fig. 1), the protein activation as a response to time-limited Ca²⁺ oscillations (Eq. (1)) is analysed in dependence on the oscillation frequency. The results for activation branch I (Eqs. (2), (3) and (5), where i = 1, 2) are presented in Fig. 2. Since the concentrations of the activated proteins increase in time in an oscillatory manner, the average protein activation during the last (5th) period is presented.

VALIDHTML

<img class=”figure large” border=”0″ alt=”Average activation of proteins in the activation branch I during the 5th …” src=”http://origin-ars.els-cdn.com/content/image/1-s2.0-S001457930501094X-gr2.gif” data-thumbEID=”1-s2.0-S001457930501094X-gr2.sml” data-imgEIDs=”1-s2.0-S001457930501094X-gr2.gif” data-fullEID=”1-s2.0-S001457930501094X-gr2.gif”>

Fig. 2.

Average activation of proteins in the activation branch I during the 5th oscillation period. At the third level, the activation curve has two maxima corresponding to the two frequencies of Ca²⁺ oscillations at which the protein is most efficiently activated. This is due to the superposition of the two activation curves from the second level.

caption

Figure options

 

VALIDHTML

Fig. 2 shows that at the first level the proteins are activated in a sigmoidal manner. Since the frequency of Ca²⁺ oscillations is changed so that the spike width remains constant (physiologically relevant), and the number of spikes is constant, the time for protein activation is the same for all frequencies of Ca²⁺ oscillations. On the other hand, by increasing the oscillation frequency, the time between Ca²⁺ spikes and, hence, the time for protein deactivation between spikes is shortened. Therefore, the average activation during the 5th period 〈z_i1〉 monotonically increases with the frequency of Ca²⁺ oscillations and becomes saturated at higher frequencies.

VALIDHTML

At the second level, the average protein activation during the 5th period (〈z_i2〉) shows a resonant dependence on the frequency of Ca²⁺ oscillations (see Fig. 2). This band-pass filter property is a consequence of the cascade structure of two chain-linked protein-binding reactions (Eqs. (2) and (3)). The non-zero concentrations of z_i1 during the interspike intervals can increase the protein activation z_i2 in the time between Ca²⁺ spikes. This is always the case when the oscillation frequency is high enough. However, by increasing the frequency, the total time of Ca²⁺ stimulation decreases and, hence, the time for the protein activation at the second level is reduced. Thus, for an optimal resonant protein activation z_i2, two conditions have to be fulfilled: (i) the frequency of Ca²⁺ oscillations should be high enough in order to have non-zero concentrations of z_i1 during the interspike intervals (the period should be close to (or shorter than) the characteristic time <img height=”18″ border=”0″ style=”vertical-align:bottom” width=”72″ alt=”View the MathML source” title=”View the MathML source” src=”http://origin-ars.els-cdn.com/content/image/1-s2.0-S001457930501094X-si10.gif”>τi

1

=

1

/ki

1

-mathContainerLoading Mathjax of Ca²⁺ dissociation from z_i1); (ii) the total time of Ca²⁺ signal should be long enough to allow a maximal protein activation z_i2.

VALIDHTML

The resonant response of protein activation at the second cascade level enables efficient selective regulation of cellular responses in dependence on the oscillation frequency. The third level of protein cascades then enables a superposition and allows a better resonance, i.e., a narrower maximum. It combines the second-level resonant frequencies at which the protein is activated. Indeed, Fig. 2 shows that the activation curve of the protein at the third level has two maxima corresponding to the two frequencies of Ca²⁺ oscillations at which the protein is most efficiently activated.

VALIDHTML

Now we consider activation branch II (Eqs. (2), (3) and (6), where i = 2, 3), which has the second primary branch in common with activation branch I. The results for branches I and II are qualitatively the same. However, because of different kinetics (see Table 1) the proteins respond optimally to other frequencies. Fig. 3 shows the activation curves of the third-level proteins in activation branches I and II together. Each of the curves has two maxima corresponding to the two frequencies of oscillations at which the proteins are most efficiently activated. However, the maxima are shifted; the cellular processes activated via branch I are most efficiently initiated with Ca²⁺ oscillation frequencies ν = 0.05 Hz and ν = 1.2 Hz, whereas the processes activated via branch II are most efficiently initiated with frequencies ν = 0.005 Hz and ν = 0.05 Hz.

VALIDHTML

<img class=”figure large” border=”0″ alt=”Selective regulation of cellular processes: (A) activation of the third-level …” src=”http://origin-ars.els-cdn.com/content/image/1-s2.0-S001457930501094X-gr3.gif” data-thumbEID=”1-s2.0-S001457930501094X-gr3.sml” data-imgEIDs=”1-s2.0-S001457930501094X-gr3.gif” data-fullEID=”1-s2.0-S001457930501094X-gr3.gif”>

Fig. 3.

Selective regulation of cellular processes: (A) activation of the third-level protein in process I with Ca²⁺ oscillation frequencies ν = 0.05 Hz and ν = 1.2 Hz, (B) activation of the third-level protein in process II with Ca²⁺ oscillation frequencies ν = 0.005 Hz and ν = 0.05 Hz. Ca²⁺ oscillations with the frequency ν = 0.05 Hz activate both processes simultaneously.

caption

Figure options

 

VALIDHTML

Since, in our example, the two activation branches (I and II) have one common primary branch (i = 2), the activation curves of the two activation branches in Fig. 3 have one maximum at the same frequency of Ca²⁺ oscillations (ν = 0.05 Hz) and two branch-specific maxima (ν = 0.005 Hz and ν = 1.2 Hz). Accordingly, in dependence on the frequency of Ca²⁺ oscillations, two cellular processes can be switched on independently of each other or simultaneously.

VALIDHTML

4. Discussion

Our results show that a two-level protein cascade can act as a band-pass filter for time-limited oscillations. This implies a new possible mechanism for band-pass filtering of cellular signals that differs from those normally used in electrical circuit design, where the band-pass filtering of sustained, theoretically infinitely long, oscillations is of primary interest. The proposed band-pass filter for time-limited cellular signals, which in some cases consist of only several spikes, is likely to be of high physiological importance. For Ca²⁺-calmodulin kinase II, for example, it has been shown experimentally that the kinase can be selectively activated by band-pass filtering of time-limited Ca²⁺ spike trains [15]. The underlying mechanism has been analysed theoretically by a four-step binding scheme [18]. Since in biological systems larger motifs are often combinations of smaller motifs [19], our model for the band-pass filter, based on a two-level protein cascade, can be seen as a basic motif providing a selective regulation of cellular processes.

VALIDHTML

In biological systems, several motifs and modules are known, acting as switches, amplifiers, filters, etc. [20]. In prokaryotes, for example, simple one- and two-component systems link external signals with cellular responses [21] and [22]. For frequency filters, a simple motif can act as a low-pass filter, never as a high-pass one, and only under special constraints as a band-pass filter [1] and [2]. Here, we provide evidence that a relatively simple motif, which would expectably act as a low-pass filter, behaves as a band-pass filter if the input oscillations are time-limited. In addition to the simplicity of the proposed band-pass filter, it is also much more robust to the choice of parameter values than those proposed previously. As stated by Arkin [1], the studied chemical systems acting as band-pass filters are admittedly artificial, since the parameter constraints are not likely to be met in biological systems.

VALIDHTML

We further show that the proposed band-pass filters can be simply combined into a network providing selective regulation of cellular processes. The number of activation branches in the network limits the total number of regulated processes, whereas the number of common primary branches at the first two levels of every activation branch determines the flexibility in a concomitant response to a given Ca²⁺ signal, i.e., the number of cellular processes that can be activated simultaneously.

VALIDHTML

 

The effectiveness of the proposed regulatory network to provide modularity in terms of enabling selective regulation of numerous cellular processes depends significantly on the variability of network proteins and their kinetics. A characteristic property of the regulatory proteins at the last cascade level is that maxima in their activation curves are slightly, though significantly shifted with respect to each other (Fig. 3). To accomplish this, the kinetic properties of proteins involved in the network have to be different, as is the case for matched pairs of proteins in bacterial two-component regulatory systems [21] and [22], for example. In plant and animal cells, it has been found experimentally that a superfamily of Ca²⁺-dependent protein kinases or calmodulin-like domain protein kinases (CDPK) exists [23]. Some authors have predicted that differences in isoforms of CDPK (in particular their sensitivity to Ca²⁺) suggest that each isoform is prone to respond only to a specific set of Ca²⁺ signals that, in dependence on the external stimulus [24], differ in their frequency of oscillations, as well as magnitude and duration. However, the difficult problem of how to test for differential activities of specific isoforms of CDPK in vivo remains unsolved [25].

VALIDHTML

Little is known about the kinetic properties of proteins that constitute intracellular signalling networks [3], [26] and [27], and also the computational function of many of the signalling networks is poorly understood [28]. However, it is clear that complex networks of signalling cascades are able to process vast amounts of external inputs, including those transmitted by various hormones and neurotransmitters, as well as signals from neighbouring cells, and selectively convert them into precise intracellular actions that regulate different processes, ranging from egg fertilisation to cell death [8] and [25]. Our study provides novel insights into how such a complex array of coherently functioning elements can be modelled mathematically with mass-action kinetics, simple spike-like oscillations, and a bow-tie architecture. This provides a generally applicable scheme that can easily be upgraded and extended to more complex and specific problems. In the future, however, additional experiments are necessary to verify model predictions and indicate ways for their improvements.

VALIDHTML

Acknowledgements

A travel grant from the Slovenian and German Ministries of Research and Education (Grant Nos. BI-DE/03-04-003 and SVN 02/013, respectively) for mutual working visits is gratefully acknowledged.

VALIDHTML

 

References

• [1]
• P. Arkin
• Signal processing by biochemical reaction networks

1. Walleczek (Ed.), Self-Organized Biodynamics and Nonlinear Control, Cambridge University Press, Cambridge, UK (2000), pp. 112–144

• [2]

1. Samoilov, A. Arkin, J. Ross

• Signal processing by simple chemical systems

1. Phys. Chem. A, 106 (2002), pp. 10205–10221

• [3]

1. Heinrich, B.G. Neel, T.A. Rapoport

• Mathematical models of protein kinase signal transduction
• Cell., 9 (2002), pp. 957–970
• [4]

1. Nakabayashi, A. Sasaki

• Optimal phosphorylation step number of intracellular signal-transduction pathway

1. Theor. Biol., 233 (2005), pp. 413–421

• [5]

1. Csete, J. Doyle

• Bow ties, metabolism and disease
• Trends Biotechnol., 22 (2004), pp. 446–450
• [6]
• W. Ma, A.P. Zeng
• The connectivity structure, giant strong component and centrality of metabolic networks
• Bioinformatics, 19 (2003), pp. 1423–1430
• [7]

1. Klein, B. Steiner, A. Steil

• Known and novel diversity approaches as a powerful means to enhance the performance of cellular mobile radio systems
• IEEE J. Sel. Area. Comm., 14 (1996), pp. 1784–1795
• [8]
• J. Berridge, M.D. Bootman, P. Lipp
• Calcium – a life and death signal
• Nature, 395 (1998), pp. 645–648
• [9]

1. Schuster, M. Marhl, T. Höfer

• Modelling of simple and complex calcium oscillations. From single-cell responses to intercellular signalling
• J. Biochem., 269 (2002), pp. 1333–1355
• [10]

1. Falcke

• Reading the patterns in living cells – the physics of Ca²⁺ signalling
• Phys., 53 (2004), pp. 255–440
• [11]

1. Quesada, F. Martin, E. Roche, B. Soria

• Nutrients induce different Ca²⁺ signals in cytosol and nucleus in pancreatic beta-cells
• Diabetes, 53 (2004), pp. S92–S95
• [12]
• L. Nixon, M. Levasseur, A. McDougall, K.T. Jones
• Ca²⁺ oscillations promote APC/C-dependent cyclin B1 degradation during metaphase arrest and completion of meiosis in fertilizing mouse eggs
• Biol., 12 (2002), pp. 746–750
• [13]
• J. Allen, S.P. Chu, C.L. Harrington, K. Schumacher, T. Hoffman, Y.Y. Tang, E. Grill, J.I. Schroeder
• A defined range of guard cell calcium oscillation parameters encodes stomatal movements
• Nature, 411 (2001), pp. 1053–1057
• [14]

1. Li, G.-X. Wang, M. Xin, H.-M. Yang, X.-J. Wu, T. Li

• The parameters of guard cell calcium oscillation encodes stomatal oscillation and closure in Vicia faba
• Plant Sci., 166 (2004), pp. 415–421
• [15]

1. De Koninck, H. Schulman

• Sensitivity of CaM kinase II to the frequency of Ca²⁺ oscillations
• Science, 279 (1998), pp. 227–230
• [16]
• -X. Li, A. Goldbeter
• Pulsatile signaling in intercellular communication
• J., 61 (1992), pp. 161–171
• [17]

1. Schuster, B. Knoke, M. Marhl

• Differential regulation of proteins by bursting calcium oscillations – a theoretical study
• BioSystems, 81 (2005), pp. 49–63
• [18]

1. Dupont, G. Houart, P. De Koninck

• Sensitivity of CaM kinase II to the frequency of Ca²⁺ oscillations: a simple model
• Cell Calcium, 34 (2003), pp. 485–497
• [19]

1. Yeger-Lotem, S. Sattath, N. Kashtan, S. Itzkovitz, R. Milo, R.Y. Pinter, U. Alon, H. Margalit

• Network motifs in integrated cellular networks of transcription-regulation and protein–protein interaction
• Natl. Acad. Sci. USA, 101 (2004), pp. 5934–5939
• [20]
• M. Wolf, A.P. Arkin
• Motifs, modules and games in bacteria
• Opin. Microbiol., 6 (2003), pp. 125–134

VALIDHTML

• [21]

1. Alves, M.A. Savageau

• Comparative analysis of prototype two-component systems with either bifunctional or monofunctional sensors: differences in molecular structure and physiological function
• Microbiol., 48 (2003), pp. 25–51
• [22]
• E. Ulrich, E.V. Koonin, I.B. Zhulin
• One-component systems dominate signal transduction in prokaryotes
• Trends Microbiol., 13 (2005), pp. 52–56
• [23]
• C. Harmon, M. Gribskov, J.F. Harper
• CDPKs – a kinase for every Ca²⁺ signal?
• Trends Plant Sci., 5 (2000), pp. 154–159
• [24]
• R. McAinsh, A.M. Hetherington
• Encoding specificity in Ca²⁺ signalling systems
• Trends Plant Sci., 3 (1998), pp. 32–36
• [25]
• E. Dumont, S. Dremier, I. Pirson, C. Maenhaut
• Cross signaling, cell specificity, and physiology
• J. Physiol. Cell Physiol., 283 (2002), pp. C2–C28
• [26]
• S. Bhalla, R. Iyengar
• Emergent properties of networks of biological signaling pathways
• Science, 283 (1999), pp. 381–387
• [27]
• V. Rao, A.P. Arkin
• Control motifs for intracellular regulatory networks
• Rev. Biomed. Eng., 3 (2001), pp. 391–419
• [28]
• M. Sauro, B.N. Kholodenko
• Quantitative analysis of signaling networks
• Biophys. Mol. Biol., 86 (2004), pp. 5–43

VALIDHTML

 

Corresponding author. Fax: +386 2 2518180.

footerNotes

VALIDHTML

Copyright © 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

VALIDHTML

 

 

 

 

 

• About ScienceDirect
• Contact and support
• Terms and conditions
• Privacy policy

 

• CSAS will be providing the links

 

Copyright © 2015 Elsevier B.V. or its licensors or contributors. ScienceDirect® is a registered trademark of Elsevier B.V.

Cookies are used by this site. To decline or learn more, visit our Cookies page.

Switch to Mobile Site

 

• footer
• sdFooter

footer-area

 

Recommended articles

• Differential regulation of proteins by bursting calcium oscillations—a theoretical study
• 2005, Biosystemsmore
• Structure of dimeric ATP synthase from mitochondria: An angular association of monomers induces the strong curvature of the inner membrane
• 2005, FEBS Lettersmore
• A minimal model for decoding of time-limited Ca²⁺ oscillations
• 2006, Biophysical Chemistrymore

• View more articles »

 

Citing articles (24)

 

Related book content