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The mitogen-activated protein kinase (MAPK) cascade is a highly conserved series of three protein kinases implicated in diverse biological processes. Here we demonstrate that the cascade arrangement has unexpected consequences for the dynamics of MAPK signaling. We solved the rate equations for the cascade numerically and found that MAPK is predicted to behave like a highly cooperative enzyme, even though it was not assumed that any of the enzymes in the cascade were regulated cooperatively. Measurements of MAPK activation in Xenopus oocyte extracts confirmed this prediction. The stimulus/response curve of the MAPK was found to be as steep as that of a cooperative enzyme with a Hill coefficient of 4-5, well in excess of that of the classical allosteric protein hemoglobin. The shape of the MAPK stimulus/ response curve may make the cascade particularly appropriate for mediating processes like mitogenesis, cell fate induction, and oocyte maturation, where a cell switches from one discrete state to another.
Alessi,
Identification of the sites in MAP kinase kinase-1 phosphorylated by p74raf-1.
1994, Pubmed
Alessi,
Identification of the sites in MAP kinase kinase-1 phosphorylated by p74raf-1.
1994,
Pubmed
Anderson,
Requirement for integration of signals from two distinct phosphorylation pathways for activation of MAP kinase.
1990,
Pubmed
Bardwell,
Signaling in the yeast pheromone response pathway: specific and high-affinity interaction of the mitogen-activated protein (MAP) kinases Kss1 and Fus3 with the upstream MAP kinase kinase Ste7.
1996,
Pubmed
Chock,
Superiority of interconvertible enzyme cascades in metabolite regulation: analysis of multicyclic systems.
1977,
Pubmed
Chock,
Interconvertible enzyme cascades in cellular regulation.
1980,
Pubmed
Cobb,
How MAP kinases are regulated.
1995,
Pubmed
Ferrell,
MAP kinases in mitogenesis and development.
1996,
Pubmed
,
Xenbase
Goldbeter,
Ultrasensitivity in biochemical systems controlled by covalent modification. Interplay between zero-order and multistep effects.
1984,
Pubmed
Goldbeter,
An amplified sensitivity arising from covalent modification in biological systems.
1981,
Pubmed
Goldbeter,
Sensitivity amplification in biochemical systems.
1982,
Pubmed
Haccard,
Induction of metaphase arrest in cleaving Xenopus embryos by MAP kinase.
1993,
Pubmed
,
Xenbase
Huang,
Constitutive activation of Mek1 by mutation of serine phosphorylation sites.
1994,
Pubmed
Huang,
Dependence of Mos-induced Cdc2 activation on MAP kinase function in a cell-free system.
1996,
Pubmed
,
Xenbase
Koshland,
Comparison of experimental binding data and theoretical models in proteins containing subunits.
1966,
Pubmed
Koshland,
Amplification and adaptation in regulatory and sensory systems.
1982,
Pubmed
Marshall,
MAP kinase kinase kinase, MAP kinase kinase and MAP kinase.
1994,
Pubmed
Matsuda,
Xenopus MAP kinase activator: identification and function as a key intermediate in the phosphorylation cascade.
1992,
Pubmed
,
Xenbase
Nebreda,
The protein kinase mos activates MAP kinase kinase in vitro and stimulates the MAP kinase pathway in mammalian somatic cells in vivo.
1993,
Pubmed
,
Xenbase
Nebreda,
The c-mos proto-oncogene protein kinase turns on and maintains the activity of MAP kinase, but not MPF, in cell-free extracts of Xenopus oocytes and eggs.
1993,
Pubmed
,
Xenbase
Pagès,
Constitutive mutant and putative regulatory serine phosphorylation site of mammalian MAP kinase kinase (MEK1).
1994,
Pubmed
Payne,
Identification of the regulatory phosphorylation sites in pp42/mitogen-activated protein kinase (MAP kinase).
1991,
Pubmed
Posada,
Requirements for phosphorylation of MAP kinase during meiosis in Xenopus oocytes.
1992,
Pubmed
,
Xenbase
Posada,
Mos stimulates MAP kinase in Xenopus oocytes and activates a MAP kinase kinase in vitro.
1993,
Pubmed
,
Xenbase
Resing,
Determination of v-Mos-catalyzed phosphorylation sites and autophosphorylation sites on MAP kinase kinase by ESI/MS.
1995,
Pubmed
Shibuya,
Mos induces the in vitro activation of mitogen-activated protein kinases in lysates of frog oocytes and mammalian somatic cells.
1993,
Pubmed
,
Xenbase
Shibuya,
Oncogenic ras triggers the activation of 42-kDa mitogen-activated protein kinase in extracts of quiescent Xenopus oocytes.
1992,
Pubmed
,
Xenbase
Yew,
Meiotic initiation by the mos protein in Xenopus.
1992,
Pubmed
,
Xenbase
Zheng,
Activation of MEK family kinases requires phosphorylation of two conserved Ser/Thr residues.
1994,
Pubmed
