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Overview
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Background
The role of mitogen-activated protein kinases (MAPKs) in cell signaling pathways is well established. The rat gene Tpl-2, for tumor progression locus 2, and the human and mouse homologues c-Cot, for cancer osaka thyroid oncogene, encode a proto-oncogene serine/threonine protein kinase that was shown to play a role in the functional activation of the MAP kinase pathway. Overexpression of Cot induces MAP kinase activation in COS-1 and NIH/3T3 cells. Cot-mediated activation of MAP kinase is inhibited by both Ras N17, a dominant negative mutant of c-H-Ras, and Raf-1s621A, a dominant negative mutant of Raf-1, suggesting that Cot functions upstream of Ras and Raf-1.Other studies have shown that a kinase-negative, dominant negative mutant of Cot partially blocks Ras or Raf-1-induced MAP kinase activation, arguing that Cot functions downstream of Ras and Raf-1.
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