Sci. STKE, 13 August 2002
Cell Biology Holistic Cell Signaling
Mitogen-activated protein (MAP) kinases 1 and 2 are important regulators of many cellular processes. Not surprisingly then, they are subject to complicated regulatory circuits that both feed forward to favor activation of the kinases and feed back by stimulating enzymes that lead to inactivation of the MAP kinases. MAP kinase phosphatase (MKP), for example, dephosphorylates--and can thus inactivate--MAP kinases 1 and 2. However, MKP must be considered in the context of competing feedback loops and other inhibitory phosphatases. Bhalla et al. (see the Perspective by Ingolia and Murray) use a combination of experimental analysis with computational analysis and modeling to propose an unexpected role for MKP. Their studies indicate that MKP is not a major determinant of the acute activity of MAP kinases in growth factor-stimulated cells. Rather, increased activity of MKP seems to change the properties of the regulatory network such that strong stimuli that should have produced sustained activation of the MAP kinases only produces a short-term activation of those enzymes.
Citation: Holistic Cell Signaling. Sci. STKE 2002, tw300 (2002).
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