Reconstruction of cellular signalling networks and analysis of their properties

Nature Reviews Molecular Cell Biology

Volumn 6, Issue 2, 2005, Pages 99-111

  Papin, Jason A ^a,b   Hunter, Tony ^c   Palsson, Bernhard O ^a   Subramaniam, Shankar ^a,d  

^a UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

^b University of Virginia   (United States)

^c SALK INSTITUTE FOR BIOLOGICAL STUDIES   (United States)

^d UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

G PROTEIN COUPLED RECEPTOR; MITOGEN ACTIVATED PROTEIN KINASE; STRESS ACTIVATED PROTEIN KINASE;

APOPTOSIS; CELL CYCLE; CELL FUNCTION; CELL INTERACTION; CELL MIGRATION; CELL PROLIFERATION; GENOME; HIGH THROUGHPUT SCREENING; PRIORITY JOURNAL; PROTEOMICS; REVIEW; SIGNAL TRANSDUCTION;

ANIMALS; CELL PHYSIOLOGY; COMPUTATIONAL BIOLOGY; COMPUTER SIMULATION; HUMANS; MODELS, BIOLOGICAL; MODELS, MOLECULAR; MODELS, THEORETICAL; PROTEIN INTERACTION MAPPING; SIGNAL TRANSDUCTION; TIME FACTORS;

EID: 13444278821     PISSN: 14710072     EISSN: None     Source Type: Journal    
DOI: 10.1038/nrm1570     Document Type: Review

References (130)

1. Finkel, T. & Gutkind, J. S. Signal transduction and human disease (Wiley-Liss, Hoboken, New Jersey, USA, 2003).
2. Li, J. et al. The Molecule Pages database. Nature 420, 716-717 (2002).
3. Levchenko, A. Dynamical and integrative cell signaling: challenges for the new biology. Biotechnol. Bioeng. 84, 773-782 (2003).
4. Weng, G., Bhalla, U. S. & Iyengar, R. Complexity in biological signaling systems. Science 284, 92-96 (1999).
5. Sivakumaran, S., Hariharaputran, S., Mishra, J. & Bhalla, U. S. The database of quantitative cellular signaling: management and analysis of chemical kinetic models of signaling networks. Bioinformatics 19, 408-415 (2003).
6. Gilman, A. G. et al. Overview of the Alliance for Cellular Signaling. Nature 420, 703-706 (2002). Provides an overview of the first coordinated, multi-institutional effort to systematically unravel the signalling mechanisms of model systems.
7. Ge, H., Walhout, A. J. & Vidal, M. Integrating 'omic' information: a bridge between genomics and systems biology. Trends Genet. 19, 551-560 (2003). Emphasizes the need for integrating and reconciling data from several experimental sources to create the most accurate representation of biochemical networks.
8. Helmke, B. P. & Schwartz, M. A. Putting the squeeze on mechanotransduction. Dev. Cell 6, 745-746 (2004).
9. Ingber, D. E. Tensegrity I. Cell structure and hierarchical systems biology. J. Cell Sci. 116, 1157-1173 (2003).
10. Ingber, D. E. Tensegrity II. How structural networks influence cellular information processing networks. J. Cell Sci. 116, 1397-1408 (2003).
11. Pennisi, E. Human genome. A low number wins the GeneSweep Pool. Science 300, 1484 (2003).
12. Hood, L. & Galas, D. The digital code of DNA. Nature 421, 444-448 (2003).
13. Vander, A. J., Sherman, J. H. & Luciano, D. S. Human physiology: the mechanisms of body function (WCB McGraw-Hill, Boston, Massachusetts, USA 1998).
14. Venter, J. C. et al. The sequence of the human genome. Science 291, 1304-1351 (2001).
15. Manning, G., Whyte, D. B., Martinez, R., Hunter, T. & Sudarsanam, S. The protein kinase complement of the human genome. Science 298, 1912-1934 (2002). The authors present the first systematic inventory of a complete set of signalling network components (protein kinases) in the human cell.
16. Wang, W. Q., Sun, J. P. & Zhang, Z. Y. An overview of the protein tyrosine phosphatase superfamily. Curr. Top. Med. Chem. 3, 739-748 (2003).
17. Forest, A. R. et al. Phosphoregulators: protein kinases and protein phosphatases of mouse. Genome Res. 13, 1443-1454 (2003).
18. Alonso, A. et al. Protein tyrosine phosphatases in the human genome. Cell 117, 699-711 (2004).
19. Lander, E. S. et al. Initial sequencing and analysis of the human genome. Nature 409, 860-921 (2001). This, and reference 14, reported the initial sequence of the human genome. They provide a glimpse into the 'parts list' of signalling networks from which further reconstructions and analyses will be developed.
20. Roberts, G. C. & Smith, C. W. Alternative splicing: combinatorial output from the genome. Curr. Opin. Chem. Biol. 6, 375-383 (2002).
21. Modrek, B. & Lee, C. A genomic view of alternative splicing. Nature Genet. 30, 13-19 (2002).
22. Thanaraj, T. A. et al. ASD: the alternative splicing database. Nucleic Acids Res. 32, D64-D69 (2004).
23. Hìrano, F. et al. Alternative splicing variants of IκBβ establish differential NF-κB signal responsiveness in human cells. Mol. Cell. Biol. 18, 2596-2607 (1998).
24. Modrek, B., Resch, A., Grasso, C. & Lee, C. Genome-wide detection of alternative splicing in expressed sequences of human genes. Nucleic Acids Res. 29, 2850-2859 (2001).
25. O'Donovan, C., Apweiler, R. & Bairoch, A. The human proteomics initiative (HPI). Trends Biotechnol. 19, 178-181 (2001).
26. Heaney, M. L. & Golde, D. W. Soluble receptors in human disease. J. Leukoc. Biol. 64, 135-146 (1998).
27. Service, R. F. Proteomics. High-speed biologists search for gold in proteins. Science 294, 2074-2077 (2001).
28. Kiekhaefer, C. M., Grass, J. A., Johnson, K. D., Boyer, M. E. & Bresnick, E. H. Hematopoietic-specific activators establish an overlapping pattern of histone acetylation and methylation within a mammalian chromatin domain. Proc. Natl Acad. Sci. USA 99, 14309-14314 (2002).
29. Fischle, W., Wang, Y. & Allis, C. D. Binary switches and modification cassettes in histone biology and beyond. Nature 425, 475-479 (2003).
30. Park, S. H., Zarrinpar, A. & Lim, W. A. Rewiring MAP kinase pathways using alternative scaffold assembly mechanisms. Science 299, 1061-1064 (2003).
31. Grigoriev, A. On the number of protein-protein interactions in the yeast proteome. Nucleic Acids Res. 31, 4157-4161 (2003).
32. Hlavacek, W. S., Faeder, J. R., Blinov, M. L., Perelson, A. S. & Goldstein, B. The complexity of complexes in signal transduction. Biotechnol. Bioeng. 84, 783-794 (2003).
33. Vassilatis, D. K. et al. The G protein-coupled receptor repertoires of human and mouse. Proc. Natl Acad. Sci. USA 100, 4903-4908 (2003).
34. Papin, J. A., Price, N. D., Wiback, S. J., Fell, D. & Palsson, B. O. Metabolic pathways in the post-genome era. Trends Biochem. Sci. 28, 250-258 (2003).
35. Bomheimer, S. J., Maurya, M. R., Farquhar, M. G. & Subramaniam, S. Computational modeling reveals how interplay between components of the GTPase-cycle module regulates signal transduction. Proc. Natl Acad. Sci. USA 101, 15899-15904 (2004).
36. Schoebert, B., Eichler-Jonsson, C., Gilles, E. D. & Muller, G. Computational modeling of the dynamics of the MAP kinase cascade activated by surface and internalized EGF receptors. Nature Biotechnol. 20, 370-375 (2002).
37. Kholodenko, B. N., Demin, O. V., Moehren, G. & Hoek, J. B. Quantification of short term signaling by the epidermal growth factor receptor. J. Biol. Chem. 274, 30169-30181 (1999).
38. Masui, H., Castro, L. & Mendelsohn, J. Consumption of EGF by A431 cells: evidence for receptor recycling. J. Cell Biol. 120, 85-93 (1993).
39. Buss, J. E., Kudlow, J. E., Lazar, C. S. & Gill, G. N. Altered epidermal growth factor (EGF)-stimulated protein kinase activity in variant A431 cells with altered growth responses to EGF. Proc. Natl Acad. Sci. USA 79, 2574-2578 (1982).
40. Handin, R. I., Lux, S. E. & Stossel, T. P. Blood: principles and practice of hematology (Lippincott Williams & Wilkins, Philadelphia, USA, 2003).
41. Maxfield, F. R. & McGraw, T. E. Endocytic recycling. Nature Rev. Mol. Cell Biol. 5, 121-132 (2004).
42. Wang, Y., Pennock, S. D., Chen, X., Kazlauskas, A. & Wang, Z. Platelet-derived growth factor receptor-mediated signal transduction from endosomes. J. Biol. Chem. 279, 8038-8046 (2004).
43. Bomsztyk, K., Stanton, T. H., Smith, L. L., Rachie, N. A. & Dower, S. K. Properties of interleukin-1 and interferon-γ receptors in B lymphoid cell line. J. Biol. Chem. 264, 6052-6057 (1989).
44. Alberts, B. Molecular biology of the cell 4th edn (Garland Science, New York, 2002).
45. Savinell, J. M., Lee, G. M. & Palsson, B. O. On the orders of magnitude of epigenic dynamics and monoclonal-antibody production. Bioproc. Eng. 4, 231-234 (1989).
46. Francis, K. & Palsson, B. O. Effective intercellular communication distances are determined by the relative time constants for cyto/chemokine secretion and diffusion. Proc. Natl Acad. Sci. USA 94, 12258-12262 (1997).
47. Ramirez-Weber, F. A. & Kornberg, T. B. Cytonemes: cellular processes that project to the principal signaling center in Drosophila imaginal discs. Cell 97, 599-607 (1999).
48. Reed, J. L., Vo, T. D., Schilling, C. H. & Palsson, B. O. An expanded genome-scale model of Escherichia coli K-12 (IJR904 GSM/GPR). Genome Biol. 4, R54 (2003).
49. van Drogen, F., Stucke, V. M., Jonitsma, G. & Peter, M. MAP kinase dynamics in response to pheromones in budding yeast. Nature Cell Biol. 3, 1051-1059 (2001).
50. Kusari, A. B., Molina, D. M., Sabbagh, W. Jr., Lau, C. S. & Bardwell, L. A conserved protein interaction network involving the yeast MAP kinases Fus3 and Kssf. J. Cell Biol. 164, 267-277 (2004).
51. Wiley, H. S., Shvartsman, S. Y. & Lauffenburger, D. A. Computational modeling of the EGF-receptor system: a paradigm for systems biology. Trends Cell Biol. 13, 43-50 (2003). This review recounts the success of models of the EGF-receptor signalling system and argues for integrative computational and experimental approaches for dissecting signalling mechanisms.
52. Milo, R. et al. Network motits: simple building blocks of complex networks. Science 298, 824-827 (2002).
53. Rives, A. W. & Galitski, T. Modular organization of cellular networks. Proc. Natl Acad. Sci. USA 100, 1128-1133 (2003).
54. Hartwell, L. H., Hopfield, J. J., Leibler, S. & Murray, A. W. From molecular to modular cell biology. Nature 402, C47-C52 (1999).
55. Yi, T. M., Huang, Y., Simon, M. I. & Doyle, J. Robus1 perfect adaptation in bacterial chemotaxis through integral feedback control. Proc. Natl Acad. Sci. USA 97, 4649-4653 (2000).
56. McAdams, H. H. & Shapiro, L. A bacterial cell-cycle regulatory network operating in time and space. Science 301, 1874-1877 (2003).
57. Saucerman, J. J., Brunton, L. L., Michailova, A. P. & McCulloch, A. D. Modeling β-adrenergic control of cardiac myocyte contractility in silico. J. Biol. Chem. 278, 47997-48003 (2003).
58. Lucas, P. C., McAllister-Lucas, L. M. & Nunez, G. NF-κB signaling in lymphocytes: a new cast of characters. J. Cell Sci. 117, 31-39 (2004).
59. Cortassa, S., Aon, M. A., Marban, E., Winslow, R. L. & O'Rourke, B. An integrated model of cardiac mitochondrial energy metabolism and calcium dynamics. Biophys. J. 84, 2734-2755 (2003).
60. Spirin, V. & Mimy, L. A. Protein complexes and functional modules in molecular networks. Proc. Natl Acad. Sci. USA 100, 12123-12128 (2003).
61. Kauffman, K. J., Prakash, P. & Edwards, J. S. Advances in flux balance analysis. Curr. Opin. Biotechnol. 14, 491-496 (2003).
62. Price, N. D., Papin, J. A., Schilling, C. H. & Palsson, B. O. Genome-scale microbial in silico models: the constraints-based approach. Trends Biotechnol. 21, 162-169 (2003).
63. Ren, B. et al. Genome-wide location and function of DNA binding proteins. Science 290, 2306-2309 (2000).
64. Odom, D. T. et al. Control of pancreas and liver gene expression by HNF transcription factors. Science 303, 1378-1381 (2004).
65. Zhu, H. & Snyder, M. 'Omic' approaches for unraveling signaling networks. Curr. Opin. Cell Biol. 14, 173-179 (2002).
66. Graves, P. R. & Haystead, T. A. A functional proteomics approach to signal transduction. Recent Prog. Horm. Res. 58, 1-24 (2003).
67. von Mering, C. et al. Comparative assessment of large-scale data sets of protein-protein interactions. Nature 417, 399-403 (2002).
68. Stagljar, I., Korostensky, C., Johnsson, N. & te Heesen, S. A genetic system besed on split-ubiquitin for the analysis of interactions between membrane proteins in vivo. Proc. Natl Acad. Sci. USA 95, 5187-5192 (1998).
69. Aronheim, A., Zandi, E., Hennemann, H., Elledge, S. J. & Karin, M. Isolation of an AP-1 repressor by a novel method for detecting protein-protein interactions. Mol. Cell. Biol. 17, 3094-3102 (1997).
70. Gavin, A. C. et al. Functional organization of the yeast proteome by systematic analysis of protein complexes. Nature 415, 141-147 (2002).
71. Ho, Y. et al. Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry. Nature 415, 180-183 (2002).
72. Stagljar, I. Finding partners: emerging protein interaction technologies applied to signaling networks. Sci. STKE pe56 (2003).
73. Blagoev, B., Ong, S. E., Kratchmarova, I. & Mann, M. Temporal analysis of phosphotyrosine-dependent signaling networks by quantitative proteomics. Nature Biotechnol. 22, 1139-1145 (2004).
74. Ideker, T. et al. Integrated genomic and proteomic analyses of a systematically perturbed metabolic network. Science 292, 929-934 (2001). The authors present an approach for systematically interrogating a biochemical network.
75. Lum, L. et al. Identification of Hedgehog pathway components by RNAi in Drosophila cultured cells. Science 299, 2039-2045 (2003).
76. Brummelkamp, T. R., Nijman, S. M., Dirac, A. M. & Bernards, R. Loss of the cylindromatosis tumour suppressor inhibits apoptosis by activating NF-κB. Nature 424, 797-801 (2003).
77. Zheng, L. et al. An approach to genomewide screens of expressed small interfering RNAs in mammalian cells. Proc. Natl Acad Sci. USA 101, 135-140 (2004).
78. Boutros, M. et al. Genome-wide RNAi analysis of growth and viability in Drosophila cells. Science 303, 832-835 (2004).
79. Nielsen, U. B., Cardone, M. H., Sinskey, A. J., MacBeath, G. & Sorger, P. K. Profiling receptor tyrosine kinase activation by using Ab microarrays. Proc. Natl Acad. Sci. USA 100, 9330-9335 (2003).
80. Phair, R. D. & Misteli, T. Kinetic modelling approaches to in vivo imaging. Nature Rev. Mol. Cell Biol. 2, 898-907 (2001).
81. Meyer, T. & Teruel, M. N. Fluorescence imaging of signaling networks. Trends Cell Biol. 13, 101-106 (2003).
82. Ding, D. Q. et al. Large-scale screening of intracellular protein localization in living fission yeast cells by the use of a GFP-fusion genomic DNA library. Genes Cells 5, 169-190 (2000).
83. Huh, W. K. et al. Global analysis of protein localization in budding yeast. Nature 425, 686-691 (2003).
84. Martin-Fernandez, M., Clarke, D. T., Tobin, M. J., Jones, S. V. & Jones, G. R. Preformed oligomeric epidermal growth factor receptors undergo an ectodomain structure change during signaling. Biophys. J. 82, 2415-2427 (2002).
85. Bunemann, M., Frank, M. & Lohse, M. J. Gi protein activation in intact cells involves subunit rearrangement rather than dissociation. Proc. Natl Acad. Sci. USA 100, 16077-16082 (2003).
86. Sato, M., Ozawa, T., Inukai, K., Asano, T. & Umezawa, Y. Fluorescent indicators for imaging protein phosphorylation in single living cells. Nature Biotechnol. 20, 287-294 (2002).
87. Walhout, A. J. et al. Integrating interactome, phenome, and transcriptome mapping data for the C. elegans germline. Curr. Biol. 12, 1952-1958 (2002).
88. Herrgard, M. J., Covert, M. W. & Palsson, B. O. Reconciling gene expression data with known genome-scale regulatory network structures. Genome Res. 13, 2423-2434 (2003).
89. Plavec, I. et al. Method for analyzing signaling networks in complex cellular systems. Proc. Natl Acad. Sci. USA 101, 1223-1228 (2004).
90. Tewari, M. et al. Systematic interactome mapping and genetic perturbation analysis of a C. elegans TGF-β signaling network. Mol. Cell 13, 469-482 (2004).
91. Bouwmeester, T. et al. A physical and functional map of the human TNF-α/NF-κB signal transduction pathway. Nature Cell Biol. 6, 97-105 (2004). High-throughput experimental technologies are beginning to be used to interrogate signalling networks at a cellular level, as shown in this reference and in reference 87.
92. Sambrano, G. R. et al. Unravelling the signal-transduction network in B lymphocytes. Nature 420, 708-710 (2002).
93. Sambrano, G. R. et al. Navigating the signalling network in mouse cardiac myocytes. Nature 420, 712-714 (2002).
94. Jeong, H., Mason, S. P., Barabasi, A. L. & Oltvai, Z. N. Lethality and centrality in protein networks. Nature 411, 41-42 (2001).
95. Bu, D. et al. Topological structure analysis of the protein-protein interaction network in budding yeast. Nucleic Acids Res. 31, 2443-2450 (2003).
96. Schuster, S., Kholodenko, B. N. & Westerhoff, H. V. Cellular information transfer regarded from a stoichiometry and control analysis perspective. Biosystems 55, 73-81 (2000).
97. Papin, J. A. & Palsson, B. O. The JAK-STAT signaling network in the human B-cell: an extreme signaling pathway analysis. Biophys. J. 87, 37-46 (2004).
98. Goodman, O. B. Jr. et al. Role of arrestins in G-protein-coupled receptor endocytosis. Adv. Pharmacol. 42, 429-433 (1998).
99. Vuong, T. M. & Chabre, M. Deactivation kinetics of the transduction cascade of vision. Proc. Natl Acad Sci. USA 88, 9813-9817 (1991).
100. Teruel, M. N. & Meyer, T. Translocation and reversible localization of signaling proteins: a dynamic future for signal transduction. Cell 103, 181-184 (2000).
101. Lillemeier, B. F., Koster, M. & Kerr, I. M. STAT1 from the cell membrane to the DNA. EMBO J. 20, 2508-2517 (2001).
102. Elowitz, M. B., Surette, M. G., Wolf, P. E., Stock, J. B. & Leibler, S. Protein mobility in the cytoplasm of Escherichia coli. J. Bacteriol. 181, 197-203 (1999).
103. Swaminathan, R., Hoang, C. P. & Verkman, A. S. Photobleaching recovery and anisotropy decay of green fluorescent protein GFP-S65T in solution and cells: cytoplasmic viscosity probed by green fluorescent protein translational and rotational diffusion. Biophys. J. 72, 1900-1907 (1997).
104. Allan, V. Membrane traffic motors. FEBS Lett. 369, 101-106 (1995).
105. Theurkauf, W. E. Premature microtubule-dependent cytoplasmic streaming in cappuccino and spire mutant oocytes. Science 265, 2093-2096 (1994).
106. Stryer, L. Biochemistry (W. H. Freeman, New York, 1995).
107. Neves, S. R., Ram, P. T. & Iyengar, R. G protein pathways. Science 296, 1636-1639 (2002).
108. Zubay, G. In vitro synthesis of protein in microbial systems. Annu. Rev. Genet. 7, 267-287 (1973).
109. Rivett, A. J. Regulation of intracellular protein turnover: covalent modification as a mechanism of marking proteins for degradation. Curr. Top. Cell Regul. 28, 291-337 (1986).
110. McAdams, H. H. & Arkin, A. Simulation of prokaryotic genetic circuits. Annu. Rev. Biophys. Biomol. Struct. 27, 199-224 (1996).
111. Chang, D. Z., Wu, Z. & Ciardelli, T. L. A point mutation in interleukin-2 that alters ligand internalization. J. Biol. Chem. 271, 13349-13355 (1996).
112. Ferguson, S. S. Evolving concepts in G protein-coupled receptor endocytosis: the role in receptor desensitization and signaling. Pharmacol. Rev. 53, 1-24 (2001).
113. Jullien, J., Guili, V., Reichardt, L. F. & Rudkin, B. B. Molecular kinetics of nerve growth factor receptor trafficking and activation. J. Biol. Chem. 277, 38700-38708 (2002).
114. Resat, H., Wiley, H. S. & Dixon, D. A. Probability-weighted dynamic Monte Carlo method for reaction kinetics simulations. J. Phys. Chem. B 105, 11026-11034 (2001).
115. Bailey, J. E. Complex biology with no parameters. Nature Biotechnol. 19, 503-504 (2001).
116. Bhalla, U. S. & Iyengar, R. Emergent properties of networks of biological signaling pathways. Science 283, 381-387 (1999). Describes some of the first large-scale analyses of signalling reactions.
117. Hoffmann, A., Levchenko, A., Scott, M. L. & Baltimore, D. The IκkB-NF-κB signaling module: temporal control and selective gene activation. Science 298, 1241-1245 (2002). Shows the powerful integration of mathematical modelling with experimental investigation.
118. Lee, E., Salic, A., Kruger, R., Heinrich, R. & Kirschner, M. W. The roles of APC and Axin derived from experimental and theoretical analysis of the Wnt pathway. PLoS Biol. 1, 116-132 (2003).
119. Bartel, D. P. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116, 281-297 (2004).
120. Forster, J., Famili, I., Fu, P., Palsson, B. B. & Nielsen, J. Genome-scale reconstruction of the Saccharomyces cerevisiae metabolic network. Genome Res. 13, 244-253 (2003).
121. Davidson, E. H. et al. A genomic regulatory network for development. Science 295, 1669-1678 (2002).
122. Steffen, M., Petti, A., Aach, J., D'Haeseleer, P. & Church, G. Automated modelling of signal transduction networks. BMC Bioinformatics 3, 34 (2002).
123. Krauthammer, M. et al. Of truth and pathways: chasing bits of information through myriads of articles. Bioinformatics 18 (Suppl. 1), S249-S257 (2002).
124. Cohen, P. Protein kinases - the major drug targets of the twenty-first century? Nature Rev. Drug Discov. 1, 309-315 (2002).
125. Dancey, J. & Sausville, E. A. Issues and progress with protein kinase inhibitors for cancer treatment. Nature Rev. Drug Discov. 2, 296-313 (2003).
126. Lazebnik, Y. Can a biologist fix a radio? - Or, what I learned while studying apoptosis. Cancer Cell 2, 179-182 (2002).
127. Branden, C. & Tooze, J. Introduction to protein structure (Garland Pub., New York, USA, 1999).
128. Giannakakou, P. et al. p53 is associated with cellular microtubules and is transported to the nucleus by dynein. Nature Cell Biol. 2, 709-717 (2000).
129. Devreotes, P. & Janetopoulos, C. Eukaryotic chemotaxis: distinctions between directional sensing and polarization. J. Biol. Chem. 278, 20445-20448 (2003).
130. Heuser, J. E. & Salpeter, S. R. Organization of acetylcholine receptors in quick-frozen, deep-etched, and rotary-replicated Torpedo postsynaptic membrane. J. Cell Biol. 82, 150-173 (1979).