MAP kinases and CDKs: kinetic basis for catalytic activation.
Protein kinases constitute one of the largest enzyme families encoded by the human genome. Owing to their critical role in virtually all aspects of signal transduction, protein kinases have evolved stringent mechanisms for their regulation, which classically falls into two categories: regulation by pseudosubstrate autoinhibitory domains, and remodeling of the catalytic core in response to phosphorylation and/or protein/protein interactions. While the action of pseudosubstrate domains can be explained by simple competitive autoinhibition kinetics, it is less well understood how active site phosphorylation and/or protein/protein interactions alter rates of catalysis. Here, the kinetic basis for kinase activation is discussed in relation to the MAP kinase, ERK2, and the cyclin-dependent kinase, CDK2/cyclin A, two enzymes of central importance to mammalian cell growth and division, and which serve as prototypic models of nonautoinhibitory regulation.
Lew
John
J
Department of Molecular, Cell & Developmental Biology, Biomolecular Sciences & Engineering Program, University of California, Santa Barbara, California 92106, USA. lew@lifesci.ucsb.edu
D000818:Animals; D002384:Catalysis; D018844:Cyclin-Dependent Kinases / Q000737:chemistry* / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D007700:Kinetics; D020928:Mitogen-Activated Protein Kinases / Q000737:chemistry* / Q000378:metabolism*
D018844:Cyclin-Dependent Kinases; D020928:Mitogen-Activated Protein Kinases