The DOI matches its Crossref record; 24 of the 24 references it cites were found in a registry or an index.
MAP Kinase Phosphatase As a Locus of Flexibility in a Mitogen-Activated Protein Kinase Signaling Network
Abstract
Intracellular signaling networks receive and process information to control cellular machines. The mitogen-activated protein kinase (MAPK) 1,2/protein kinase C (PKC) system is one such network that regulates many cellular machines, including the cell cycle machinery and autocrine/paracrine factor synthesizing machinery. We used a combination of computational analysis and experiments in mouse NIH-3T3 fibroblasts to understand the design principles of this controller network. We find that the growth factor–stimulated signaling network containing MAPK 1, 2/PKC can operate with one (monostable) or two (bistable) stable states. At low concentrations of MAPK phosphatase, the system exhibits bistable behavior, such that brief stimulus results in sustained MAPK activation. The MAPK-induced increase in the amounts of MAPK phosphatase eliminates the prolonged response capability and moves the network to a monostable state, in which it behaves as a proportional response system responding acutely to stimulus. Thus, the MAPK 1, 2/PKC controller network is flexibly designed, and MAPK phosphatase may be critical for this flexible response.
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Cites
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
The mitogen-activated protein kinase signal transduction pathway
Davis, R. J. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)82362-6 · Cited by 2,139
cPLA2 is phosphorylated and activated by MAP kinase
Lin, L.-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 1,849
Emergent Properties of Networks of Biological Signaling Pathways
Bhalla, U. S., & Iyengar, R. (1999) · Science · doi:10.1126/science.283.5400.381 · Cited by 1,686
Self-citationSun, H., Charles, C. H., Lau, L. F., & Tonks, N. K. (1993) · Cell · doi:10.1016/0092-8674(93)90383-2 · Cited by 1,156
Mitogen-activated protein kinases p42mapk and p44mapk are required for fibroblast proliferation.
Pagès, G., Lenormand, P., L'Allemain, G., Chambard, J. C., Meloche, S., & Pouysségur, J. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.18.8319 · Cited by 984
Wood, K. W., Sarnecki, C., Roberts, T. M., & Blenis, J. (1992) · Cell · doi:10.1016/0092-8674(92)90076-o · Cited by 903
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 742
Protein molecules as computational elements in living cells
Bray, D. (1995) · Nature · doi:10.1038/376307a0 · Cited by 740
Increase of the Catalytic Activity of Phospholipase C-γ1 by Tyrosine Phosphorylation
Nishibe, S., Wahl, M. I., Hernandez-Sotomayor, S. M., Tonks, N. K., Rhee, S. G., & Carpenter, G. (1990) · Science · doi:10.1126/science.1700866 · Cited by 635
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Network biology: understanding the cell's functional organization
Barabási, A.-L., & Oltvai, Z. N. (2004) · Nature Reviews Genetics · doi:10.1038/nrg1272 · Cited by 7,903
Cell-signalling dynamics in time and space
Kholodenko, B. N. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1838 · Cited by 1,347
A positive-feedback-based bistable ‘memory module’ that governs a cell fate decision.
Xiong, W., & Ferrell, J. E. (2003) · Nature · doi:10.1038/nature02089 · Cited by 741
Physicochemical modelling of cell signalling pathways
Aldridge, B. B., Burke, J. M., Lauffenburger, D. A., & Sorger, P. K. (2006) · Nature Cell Biology · doi:10.1038/ncb1497 · Cited by 592
Dual‐specificity MAP kinase phosphatases (MKPs): Shaping the outcome of MAP kinase signalling
Caunt, C. J., & Keyse, S. M. (2013) · The FEBS Journal · doi:10.1111/j.1742-4658.2012.08716.x · Cited by 535
Metadata
- Authors
- Bhalla, U. S., Ram, P. T., & Iyengar, R.
- Venue
- Science
- Published
- 2002-08-09
- Volume
- 297
- Issue
- 5583
- Pages
- 1018-1023
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2101744311
- Cited by
- 631
- References
- 24
- FWCI
- 18.25
- Type
- journal article
- Language
- en
- Open access
- closed
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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