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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Protein Aliases: augmented in rheumatoid arthritis 2; Cancer Osaka thyroid oncogene; cancer Osaka thyroid, oncogene; cot (cancer Osaka thyroid) oncogene; COT proto-oncogene serine/threonine-protein kinase; EC 184.108.40.206; Ewing sarcoma transformant; mitogen activated protein kinase kinase kinase 8; Mitogen-activated protein kinase kinase kinase 8; Proto-oncogene c-Cot; proto-oncogene serine/threoine protein kinase; serine/threonine kinase (Tpl-2); Serine/threonine-protein kinase cot; TH isoform 3; TH isoform a; TH-4; TPL-2; Tumor progression locus 2; TY3H; TYH; Tyrosine 5-monooxygenase; tyrosine hydroxylase
Gene Aliases: AURA2; c-COT; COT; Cot/Tpl2; D17TPL2; EST; ESTF; MAP3K8; MEKK8; Tpl-2; TPL2