Decision Making in Cells

Cellular signal transduction networks are structured in a highly complex manner that strongly suggests they have functions beyond simply passing information from the outside of the cell to the interior. Recent evidence from mathematical and systems approaches to the study of these networks indicates that these complex networks might actually process external signals in a nontrivial way, endowing the cell emergent-decision making ability. In this chapter, we will first analyze the concepts of information, information processing, and decision making from a quantitative perspective. We will then apply that analysis to the structures and functions of intracellular signal transduction networks and see that they have many features that are consistent with nontrivial decision-making systems.

[1]  Hong Sun,et al.  MKP-1 (3CH134), an immediate early gene product, is a dual specificity phosphatase that dephosphorylates MAP kinase in vivo , 1993, Cell.

[2]  T. Coleman,et al.  Cell cycle regulation of a Xenopus Wee1-like kinase. , 1995, Molecular biology of the cell.

[3]  Zhong Mai,et al.  Boolean network-based analysis of the apoptosis network: irreversible apoptosis and stable surviving. , 2009, Journal of theoretical biology.

[4]  T. Coleman,et al.  Myt1: A Membrane-Associated Inhibitory Kinase That Phosphorylates Cdc2 on Both Threonine-14 and Tyrosine-15 , 1995, Science.

[5]  J. Ferrell.  Self-perpetuating states in signal transduction: positive feedback, double-negative feedback and bistability. , 2002, Current opinion in cell biology.

[6]  M. Cotton,et al.  G protein-coupled receptors stimulation and the control of cell migration. , 2009, Cellular signalling.

[7]  Henrik Flyvbjerg,et al.  An order parameter for networks of automata , 1988 .

[8]  B. Kholodenko,et al.  Negative feedback and ultrasensitivity can bring about oscillations in the mitogen-activated protein kinase cascades. , 2000, European journal of biochemistry.

[9]  Onn Brandman,et al.  Feedback Loops Shape Cellular Signals in Space and Time , 2008, Science.

[10]  James P. Crutchfield,et al.  Revisiting the Edge of Chaos: Evolving Cellular Automata to Perform Computations , 1993, Complex Syst..

[11]  Y Nishizuka,et al.  Synergistic action of diacylglycerol and unsaturated fatty acid for protein kinase C activation: its possible implications. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[12]  Dennis Bray,et al.  Swimming patterns and dynamics of simulated Escherichia coli bacteria , 2009, Journal of The Royal Society Interface.

[13]  Christopher G. Langton,et al.  Computation at the edge of chaos: Phase transitions and emergent computation , 1990 .

[14]  Ann M Stock,et al.  Molecular Information Processing: Lessons from Bacterial Chemotaxis* , 2002, The Journal of Biological Chemistry.

[15]  Jacques Demongeot,et al.  Roles of positive and negative feedback in biological systems. , 2002, Comptes rendus biologies.

[16]  C. E. SHANNON,et al.  A mathematical theory of communication , 1948, MOCO.

[17]  J. Doyle,et al.  Robust perfect adaptation in bacterial chemotaxis through integral feedback control. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[18]  M. Simon,et al.  Signal transduction pathways involving protein phosphorylation in prokaryotes. , 1991, Annual review of biochemistry.

[19]  E. A. Sykes,et al.  Cell–cell interaction networks regulate blood stem and progenitor cell fate , 2009, Molecular systems biology.

[20]  A. Fisher.  Opinion-decision making in the immune system: Cellular identity and lineage choice , 2002, Nature Reviews Immunology.

[21]  W. Schamel,et al.  Signal transduction: specificity of growth factors explained by parallel distributed processing. , 1996, Medical hypotheses.

[22]  S. Kauffman.  Metabolic stability and epigenesis in randomly constructed genetic nets. , 1969, Journal of theoretical biology.

[23]  J. Stock,et al.  Information Processing in Bacterial Chemotaxis , 2002, Science's STKE.

[24]  J E Ferrell,et al.  The biochemical basis of an all-or-none cell fate switch in Xenopus oocytes. , 1998, Science.

[25]  L. Kornberg,et al.  Signal transduction by cell adhesion receptors. , 1995, Biochimica et biophysica acta.

[26]  U. Alon,et al.  Robustness in bacterial chemotaxis , 2022 .

[27]  D. Bray.  Molecular Networks: The Top-Down View , 2003, Science.

[28]  T. Helikar,et al.  Emergent decision-making in biological signal transduction networks , 2008, Proceedings of the National Academy of Sciences.

[29]  Prahlad T. Ram,et al.  Formation of Regulatory Patterns During Signal Propagation in a Mammalian Cellular Network , 2005, Science.

[30]  Kenji Oosawa,et al.  Phosphorylation of three proteins in the signaling pathway of bacterial chemotaxis , 1988, Cell.

[31]  M. Marchesi,et al.  Scaling and criticality in a stochastic multi-agent model of a financial market , 1999, Nature.

[32]  L Glass,et al.  Counting and classifying attractors in high dimensional dynamical systems. , 1996, Journal of theoretical biology.

[33]  Kensuke Fukuda,et al.  Origin of critical behavior in Ethernet traffic , 2000 .

[34]  Luay Nakhleh,et al.  Hypothesis Generation in Signaling Networks , 2006, J. Comput. Biol..

[35]  A. Levchenko.  Dynamical and integrative cell signaling: challenges for the new biology , 2003, Biotechnology and bioengineering.

[36]  E. Reddy,et al.  Signaling by dual specificity kinases , 1998, Oncogene.

[37]  Y. Nishizuka.  Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C. , 1992, Science.

[38]  Eduardo Sontag,et al.  Untangling the wires: A strategy to trace functional interactions in signaling and gene networks , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[39]  D. Blair,et al.  How bacteria sense and swim. , 1995, Annual review of microbiology.

[40]  Stephen L. Abrams,et al.  Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation and drug resistance. , 2007, Biochimica et biophysica acta.

[41]  Simon Haykin,et al.  Neural Networks: A Comprehensive Foundation , 1998 .

[42]  Young,et al.  Inferring statistical complexity. , 1989, Physical review letters.

[43]  R. Solé,et al.  Lyapunov exponents in random Boolean networks , 1999, adap-org/9907001.

[44]  Benjamin L Turner,et al.  Supporting Online Material Materials and Methods Som Text Figs. S1 to S3 Table S1 References Robust, Tunable Biological Oscillations from Interlinked Positive and Negative Feedback Loops , 2022 .

[45]  D. Bray,et al.  Intracellular signalling as a parallel distributed process. , 1990, Journal of theoretical biology.

[46]  Stuart A. Kauffman,et al.  ORIGINS OF ORDER , 2019, Origins of Order.

[47]  Wentian Li,et al.  On the Relationship between Complexity and Entropy for Markov Chains and Regular Languages , 1991, Complex Syst..

[48]  J. Konvalina,et al.  COMBINATORIAL FRACTAL GEOMETRY WITH A BIOLOGICAL APPLICATION , 2006 .

[49]  J. Tschopp,et al.  Life and death decisions: secondary complexes and lipid rafts in TNF receptor family signal transduction. , 2004, Immunity.

[50]  A. Persidis.  Signal transduction as a drug-discovery platform , 1998, Nature Biotechnology.

[51]  S. Huang,et al.  Genomics, complexity and drug discovery: insights from Boolean network models of cellular regulation. , 2001, Pharmacogenomics.

[52]  J. Ferrell,et al.  A positive-feedback-based bistable ‘memory module’ that governs a cell fate decision , 2003, Nature.

[53]  Charles F. Hockett,et al.  A mathematical theory of communication , 1948, MOCO.

[54]  G L Johnson,et al.  Phosphorylation and activation of a high molecular weight form of phospholipase A2 by p42 microtubule-associated protein 2 kinase and protein kinase C. , 1993, The Journal of biological chemistry.

[55]  R L Juliano,et al.  Signal transduction by cell adhesion receptors and the cytoskeleton: functions of integrins, cadherins, selectins, and immunoglobulin-superfamily members. , 2002, Annual review of pharmacology and toxicology.

[56]  Steffen Klamt,et al.  A Logical Model Provides Insights into T Cell Receptor Signaling , 2007, PLoS Comput. Biol..

[57]  J. Ferrell,et al.  Bistability in the JNK cascade , 2001, Current Biology.

[58]  Bruce Perens,et al.  The emerging economic paradigm of Open Source , 2005, First Monday.

[59]  Chi-Ying F. Huang,et al.  Ultrasensitivity in the mitogen-activated protein kinase cascade. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[60]  Stephan Huveneers,et al.  Adhesion signaling – crosstalk between integrins, Src and Rho , 2009, Journal of Cell Science.

[61]  J. Pouysségur,et al.  Reduced MAP kinase phosphatase-1 degradation after p42/p44MAPK-dependent phosphorylation. , 1999, Science.

[62]  A. Bren,et al.  How Signals Are Heard during Bacterial Chemotaxis: Protein-Protein Interactions in Sensory Signal Propagation , 2000, Journal of bacteriology.

[63]  Nils Blüthgen,et al.  Mathematical Modeling Identifies Inhibitors of Apoptosis as Mediators of Positive Feedback and Bistability , 2006, PLoS Comput. Biol..

[64]  Katherine C. Chen,et al.  Sniffers, buzzers, toggles and blinkers: dynamics of regulatory and signaling pathways in the cell. , 2003, Current opinion in cell biology.

[65]  H. Othmer,et al.  Dynamic receptor team formation can explain the high signal transduction gain in Escherichia coli. , 2003, Biophysical journal.

[66]  J. Kyriakis,et al.  Making the connection: coupling of stress-activated ERK/MAPK (extracellular-signal-regulated kinase/mitogen-activated protein kinase) core signalling modules to extracellular stimuli and biological responses. , 1999, Biochemical Society symposium.

[67]  Juliano Rl.  Integrin signals and tumor growth control. , 1994 .

[68]  J. Parsons,et al.  Integrin connections map: to infinity and beyond. , 2002, Science.

[69]  G L Johnson,et al.  Organization and regulation of mitogen-activated protein kinase signaling pathways. , 1999, Current opinion in cell biology.

[70]  M. Eisenbach,et al.  Correlation between phosphorylation of the chemotaxis protein CheY and its activity at the flagellar motor. , 1992, Biochemistry.

[71]  U. Bhalla,et al.  Complexity in biological signaling systems. , 1999, Science.

[72]  Vincent Danos,et al.  Internal coarse-graining of molecular systems , 2009, Proceedings of the National Academy of Sciences.

[73]  E. Henson,et al.  Surviving cell death through epidermal growth factor (EGF) signal transduction pathways: implications for cancer therapy. , 2006, Cellular signalling.

[74]  Nils Cordes,et al.  Signalling via integrins: implications for cell survival and anticancer strategies. , 2007, Biochimica et biophysica acta.

[75]  S. Leibler,et al.  Robustness in simple biochemical networks , 1997, Nature.

[76]  D. Bray.  Protein molecules as computational elements in living cells , 1995, Nature.

[77]  T. Sugimoto,et al.  Mitogen-activated protein kinase phosphatase: a negative regulator of the mitogen-activated protein kinase cascade. , 1999, European journal of pharmacology.

[78]  B. Derrida,et al.  Phase Transitions in Two-Dimensional Kauffman Cellular Automata , 1986 .

[79]  Kwang-Hyun Cho,et al.  Coupled positive feedbacks provoke slow induction plus fast switching in apoptosis , 2007, FEBS letters.

[80]  Adam P Arkin,et al.  Design and Diversity in Bacterial Chemotaxis: A Comparative Study in Escherichia coli and Bacillus subtilis , 2004, PLoS biology.

[81]  U. Bhalla,et al.  Emergent properties of networks of biological signaling pathways. , 1999, Science.

[82]  Prahlad T. Ram,et al.  MAP Kinase Phosphatase As a Locus of Flexibility in a Mitogen-Activated Protein Kinase Signaling Network , 2002, Science.

[83]  Roger J. Davis,et al.  cPLA2 is phosphorylated and activated by MAP kinase , 1993, Cell.

[84]  Bartolome Luque,et al.  Measuring Mutual Information in Random Boolean Networks , 1999, Complex Syst..

[85]  Dennis Bray,et al.  Bacterial chemotaxis and the question of gain , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[86]  James E. Ferrell,et al.  The JNK Cascade as a Biochemical Switch in Mammalian Cells Ultrasensitive and All-or-None Responses , 2003, Current Biology.

[87]  J. S. Parkinson,et al.  Bacterial chemoreceptors: high-performance signaling in networked arrays. , 2008, Trends in biochemical sciences.

[88]  J. Sible.  Thanks for the memory , 2003 .

[89]  J. Ferrell.  Tripping the switch fantastic: how a protein kinase cascade can convert graded inputs into switch-like outputs. , 1996, Trends in biochemical sciences.