Emergent Properties of Networks of Biological Signaling Pathways
Open accessAbstract
Many distinct signaling pathways allow the cell to receive, process, and respond to information. Often, components of different pathways interact, resulting in signaling networks. Biochemical signaling networks were constructed with experimentally obtained constants and analyzed by computational methods to understand their role in complex biological processes. These networks exhibit emergent properties such as integration of signals across multiple time scales, generation of distinct outputs depending on input strength and duration, and self-sustaining feedback loops. Feedback can result in bistable behavior with discrete steady-state activities, well-defined input thresholds for transition between states and prolonged signal output, and signal modulation in response to transient stimuli. These properties of signaling networks raise the possibility that information for “learned behavior” of biological systems may be stored within intracellular biochemical reactions that comprise signaling pathways.
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Models have described the dynamics of biochemical reactions that transduce stimuli into LTP.
“In recent years, models have described the dynamics of the biochemical reactions that transduce stimuli into LTP86–88.”
From The right time to learn: Mechanisms and optimization of spaced learning (2016) · cites this paper as [86]
Simulations have reproduced the dynamics of MAPK during LTP induction.
“Simulations have reproduced the dynamics of MAPK during LTP induction80,86,88.”
From The right time to learn: Mechanisms and optimization of spaced learning (2016) · cites this paper as [86]
In model development, data from several preparation types and species commonly need to be used to estimate different parameters.
“In model development, data from several preparation types (for example, cell cultures and slices) and species (for example, primates and rodents) commonly need to be used to estimate different parameters86,88.”
From The right time to learn: Mechanisms and optimization of spaced learning (2016) · cites this paper as [86]
Cites
A synaptic model of memory: long-term potentiation in the hippocampus
Bliss, T. V. P., & Collingridge, G. L. (1993) · Nature · doi:10.1038/361031a0 · Cited by 11,566 · see citing works
Inositol trisphosphate and calcium signalling
Berridge, M. J. (1993) · Nature · doi:10.1038/361315a0 · Cited by 6,545 · see citing works
Death Receptors: Signaling and Modulation
Ashkenazi, A., & Dixit, V. M. (1998) · Science · doi:10.1126/science.281.5381.1305 · Cited by 5,866 · see citing works
Marshall, C. J. (1995) · Cell · doi:10.1016/0092-8674(95)90401-8 · Cited by 4,557 · see citing works
Intracellular Signaling by Hydrolysis of Phospholipids and Activation of Protein Kinase C
Nishizuka, Y. (1992) · Science · doi:10.1126/science.1411571 · Cited by 4,472 · see citing works
INOSITOL TRISPHOSPHATE AND DIACYLGLYCEROL: TWO INTERACTING SECOND MESSENGERS
Berridge, M. J. (1987) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.56.070187.001111 · Cited by 3,285 · see citing works
Aaronson, S. A. (1991) · Science · doi:10.1126/science.1659742 · Cited by 2,017 · see citing works
Clapham, D. E. (1995) · Cell · doi:10.1016/0092-8674(95)90408-5 · Cited by 1,960 · see citing works
cPLA2 is phosphorylated and activated by MAP kinase
Lin, L., Wartmann, M., Lin, A. Y., Knopf, J. L., Seth, A., & Davis, R. J. (1993) · Cell · doi:10.1016/0092-8674(93)90666-e · Cited by 1,851 · see citing works
Synaptic tagging and long-term potentiation
Frey, U., & Morris, R. G. M. (1997) · Nature · doi:10.1038/385533a0 · Cited by 1,736 · see citing works
Growth factor signaling by receptor tyrosine kinases
Schlessinger, J., & Ullrich, A. (1992) · Neuron · doi:10.1016/0896-6273(92)90177-f · Cited by 1,430 · see citing works
Protein kinase Cα activates RAF-1 by direct phosphorylation
Kölch, W., Heidecker, G., Kochs, G., Hummel, R., Vahidi, H., Mischak, H., Finkenzeller, G., Marmé, D., & Rapp, U. R. (1993) · Nature · doi:10.1038/364249a0 · Cited by 1,278 · see citing works
Autophosphorylation at Thr <sup>286</sup> of the α Calcium-Calmodulin Kinase II in LTP and Learning
Giese, K. P., Fedorov, N. B., Filipkowski, R. K., & Silva, A. J. (1998) · Science · doi:10.1126/science.279.5352.870 · Cited by 1,055 · see citing works
Requirement of a Critical Period of Transcription for Induction of a Late Phase of LTP
Nguyen, P. V., Abel, T., & Kandel, E. R. (1994) · Science · doi:10.1126/science.8066450 · Cited by 888 · see citing works
Miller, S. (1986) · Cell · doi:10.1016/0092-8674(86)90008-5 · Cited by 864 · see citing works
Hunter, T. R. (1991) · Cell · doi:10.1016/0092-8674(91)90637-e · Cited by 757 · see citing works
The Book of GENESIS: Exploring Realistic Neural Models with the GEneral NEural SImulation System
Bower, J. M., & Beeman, D. (1994) · Medical Entomology and Zoology · Cited by 750 · see citing works
Traub, R. D., Wong, R. K. S., Miles, R., & Michelson, H. B. (1991) · Journal of Neurophysiology · doi:10.1152/jn.1991.66.2.635 · Cited by 715 · see citing works
Calmodulin Trapping by Calcium-Calmodulin-Dependent Protein Kinase
Meyer, T., Hanson, P. I., Stryer, L., & Schulman, H. (1992) · Science · doi:10.1126/science.256.5060.1199 · Cited by 637 · see citing works
Increase of the Catalytic Activity of Phospholipase C-γ1 by Tyrosine Phosphorylation
Nishibe, S., Wahl, M. I., Hernández‐Sotomayor, S. M. T., Tonks, N. K., Rhee, S. G., & Carpenter, G. F. (1990) · Science · doi:10.1126/science.1700866 · Cited by 635 · see citing works
Neuronal Ca2+/calmodulin-dependent protein kinases.
Hanson, P., & Schulman, H. (1992) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.61.070192.003015 · Cited by 628 · see citing works
Adenylyl cyclases and the interaction between calcium and cAMP signalling
Cooper, D. M. F., Mons, N. E., & Karpen, J. W. (1995) · Nature · doi:10.1038/374421a0 · Cited by 592 · see citing works
The CaM kinase II hypothesis for the storage of synaptic memory.
Lisman, J. (1994) · Trends in Neurosciences · doi:10.1016/0166-2236(94)90014-0 · Cited by 526 · see citing works
Nemenoff, R. A., Winitz, S., Qian, N. X., Putten, V. V., Johnson, G. L., & Heasley, L. E. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)53948-x · Cited by 522 · see citing works
Hestrin, S., Nicoll, R. A., Perkel, D. J., & Sah, P. (1990) · The Journal of Physiology · doi:10.1113/jphysiol.1990.sp017980 · Cited by 491 · see citing works
Lledo, P. M., Hjelmstad, G. O., Mukherji, S., Soderling, T. R., Malenka, R. C., & Nicoll, R. A. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.24.11175 · Cited by 456 · see citing works
Protein phosphatases: recent progress.
Shenolikar, S., & Nairn, A. C. (1991) · PubMed · Cited by 392 · see citing works
Brondello, J., Brunet, A., Pouysségur, J., & McKenzie, F. R. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.2.1368 · Cited by 361 · see citing works
Pettit, D. L., Perlman, S., & Malinow, R. (1994) · Science · doi:10.1126/science.7997883 · Cited by 329 · see citing works
Postsynaptic CAMP pathway gates early LTP in hippocampal CA1 region
Blitzer, R. D., Wong, T., Nouranifar, R., Iyengar, R., & Landau, E. M. (1995) · Neuron · doi:10.1016/0896-6273(95)90018-7 · Cited by 325 · see citing works
Self-citationShinomura, T., Asaoka, Y., Oka, M., Yoshida, K., & Nishizuka, Y. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.12.5149 · Cited by 309 · see citing works
Molecular and functional diversity of mammalian G <sub>s</sub> ‐stimulated adenylyl cyclases
Iyengar, R. (1993) · The FASEB Journal · doi:10.1096/fasebj.7.9.8330684 · Cited by 299 · see citing works
Self-citationResolution of some components of adenylate cyclase necessary for catalytic activity.
Ross, E. M., & Gilman, A. G. (1977) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)66920-6 · Cited by 284 · see citing works
Chetkovich, D. M., Gray, R., Johnston, D., & Sweatt, J. D. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.15.6467 · Cited by 284 · see citing works
Role of DNA 5-Methylcytosine Transferase in Cell Transformation by fos
Bakin, A. V., & Curran, T. (1999) · Science · doi:10.1126/science.283.5400.387 · Cited by 240 · see citing works
Stimulation of specific types of Gs-stimulated adenylyl cyclases by phorbol ester treatment.
Jacobowitz, O., Chen, J., Premont, R. T., & Iyengar, R. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)53547-x · Cited by 230 · see citing works
Self-citationTHE RELATIONSHIP OF EPINEPHRINE AND GLUCAGON TO LIVER PHOSPHORYLASE
Rall, T. W., Sutherland, E. W., & Wosilait, W. D. (1956) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)65911-3 · Cited by 219 · see citing works
Carroll, M. P., & May, W. S. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)42250-2 · Cited by 215 · see citing works
Chetkovich, D. M., & Sweatt, J. D. (1993) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1993.tb09836.x · Cited by 212 · see citing works
The growth factor-inducible immediate-early gene 3CH134 encodes a protein-tyrosine-phosphatase.
Charles, C. H., Sun, H., Lau, L. F., & Tonks, N. K. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.11.5292 · Cited by 192 · see citing works
Schworer, C. M., Colbran, R. J., Keefer, J. R., & Soderling, T. R. (1988) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)68264-x · Cited by 191 · see citing works
Postsynaptic injection of Ca2+/CaM induces synaptic potentiation requiring CaMKII and PKC activity
Wang, J.-H., & Kelly, P. T. (1995) · Neuron · doi:10.1016/0896-6273(95)90048-9 · Cited by 172 · see citing works
Factors regulating the reversibility of long-term potentiation
Staubli, U., & Chun, D. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-02-00853.1996 · Cited by 169 · see citing works
Inactivation and Activation of Liver Phosphorylase
Sutherland, E. W., & Wosilait, W. D. (1955) · Nature · doi:10.1038/175169a0 · Cited by 163 · see citing works
Phorbol ester-induced stimulation and phosphorylation of adenylyl cyclase 2.
Jacobowitz, O., & Iyengar, R. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.22.10630 · Cited by 160 · see citing works
Self-citationTeng, K. K., Lander, H. M., Fajardo, J. E., Hanafusa, H., Hempstead, B. L., & Birge, R. B. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.35.20677 · Cited by 148 · see citing works
Gating by Cyclic AMP: Expanded Role for an Old Signaling Pathway
Iyengar, R. (1996) · Science · doi:10.1126/science.271.5248.461 · Cited by 126 · see citing works
Self-citationSynapse Specificity and Long-Term Information Storage
Schuman, E. M. (1997) · Neuron · doi:10.1016/s0896-6273(00)81234-9 · Cited by 99 · see citing works
The Chemistry and Biology of Cholera Toxi
Lai, C., & Kurosky, A. (1980) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238009105434 · Cited by 86 · see citing works
Schutter, E. D., & Bower, J. M. (1993) · Neural Computation · doi:10.1162/neco.1993.5.5.681 · Cited by 9 · see citing works
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Jeong, H., Tombor, B., Albert, R., Oltvai, Z. N., & Barabási, A.-L. (2000) · Nature · doi:10.1038/35036627 · Cited by 4,972 · see citing works
Critical nodes in signalling pathways: insights into insulin action
Taniguchi, C. M., Emanuelli, B., & Kahn, C. R. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1837 · Cited by 2,760 · see citing works
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Ideker, T., Galitski, T., & Hood, L. (2001) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev.genom.2.1.343 · Cited by 1,664 · see citing works
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Thattai, M., & van Oudenaarden, A. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.151588598 · Cited by 1,428 · see citing works
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Manji, H. K., Drevets, W. C., & Charney, D. S. (2001) · Nature Medicine · doi:10.1038/87865 · Cited by 1,182 · see citing works
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Gardner, T. S., di Bernardo, D., Lorenz, D., & Collins, J. J. (2003) · Science · doi:10.1126/science.1081900 · Cited by 1,117 · see citing works
Kholodenko, B. N. (2000) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.2000.01197.x · Cited by 643 · see citing works
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HUDMON, A., & SCHULMAN, H. (2002) · Biochemical Journal · doi:10.1042/bj20020228 · Cited by 615 · see citing works
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Shorter, J., & Lindquist, S. (2005) · Nature Reviews Genetics · doi:10.1038/nrg1616 · Cited by 555 · see citing works
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Heinrich, R., Neel, B. G., & Rapoport, T. A. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00528-2 · Cited by 511 · see citing works
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Sejnowski, T. J., & Destexhe, A. (2000) · Brain Research · doi:10.1016/s0006-8993(00)03007-9 · Cited by 489 · see citing works
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DESTEXHE, A., & SEJNOWSKI, T. J. (2003) · Physiological Reviews · doi:10.1152/physrev.00012.2003 · Cited by 241 · see citing works
HATAKEYAMA, M., KIMURA, S., NAKA, T., KAWASAKI, T., YUMOTO, N., ICHIKAWA, M., KIM, J.-H., SAITO, K., SAEKI, M., SHIROUZU, M., et al. (2003) · Biochemical Journal · doi:10.1042/bj20021824 · Cited by 233 · see citing works
Singh, D. K., Kumar, D., Siddiqui, Z., Basu, S. K., Kumar, V., & Rao, K. V. S. (2005) · Cell · doi:10.1016/j.cell.2005.02.036 · Cited by 206 · see citing works
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NetPyNE, a tool for data-driven multiscale modeling of brain circuits
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- Authors
- Bhalla, U. S., & Iyengar, R.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Venue
- Science
- Published
- 1999-01-15
- Volume
- 283
- Issue
- 5400
- Pages
- 381-387
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2133667940
- Cited by
- 1,686
- References
- 50
- Citations by year
- 2026: 18 · 2025: 38 · 2024: 36 · 2023: 52 · 2022: 36 · 2021: 39 · 2020: 35 · 2019: 43 · 2018: 42 · 2017: 41 · 2016: 31 · 2015: 49 · 2014: 63 · 2013: 58 · 2012: 75
- FWCI
- 29.97
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Science (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM054508, GM54508)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
- Keywords
- signaling networks, emergent properties, signal integration, feedback loops, bistability, self-excited vibration, signal transduction, learned behavior
- MeSH terms
- Cyclic AMP, Animals, Calcium, Computer Simulation, Enzyme Activation, Epidermal Growth Factor, Feedback, Isoenzymes, Kinetics, Memory, Models, Biological, Neurons, Type C Phospholipases, Phosphoprotein Phosphatases, Phosphorylation, Protein Kinase C, Synapses, Second Messenger Systems, Signal Transduction, Receptors, N-Methyl-D-Aspartate, Protein Tyrosine Phosphatases, Long-Term Potentiation, Calcium-Calmodulin-Dependent Protein Kinases, Immediate-Early Proteins, Cell Cycle Proteins, Calcineurin, Phospholipase C gamma, Dual Specificity Phosphatase 1, Protein Phosphatase 1, Calcium-Calmodulin-Dependent Protein Kinase Type 2, ErbB Receptors
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