Cited by 1,686Gene Regulatory Network AnalysisBioinformatics and Genomic NetworksMicrobial Metabolic Engineering and Bioproduction

Emergent Properties of Networks of Biological Signaling Pathways

Open access
Bhalla, Upinder S., Iyengar, Ravi·1999·Science

Abstract

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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Crossref · 10.1126/science.283.5400.381

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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.”
  • Simulations have reproduced the dynamics of MAPK during LTP induction.

    “Simulations have reproduced the dynamics of MAPK during LTP induction80,86,88.”
  • 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.”

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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
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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