mitogen-activated protein kinase kinase kinase 8 (MAP3K8, cot proto-oncogene protein, cot kinase, Cot/Tpl-2, cancer Osaka thyroid oncogene protein, ESTF)
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Function
- stimulates both ERK & JNK pathways
- involved in CD3/CD28 induction of NF kappa-B, upstream of NIK (NF kappa-B inducing kinase)
- able to activate NF-kappa-B 1 by stimulating proteasome- mediated proteolysis of NF-kappa-B 1/p105
- plays a role in the cell cycle
- longer form of cot has some transforming activity, although it is much weaker than the activated cot oncoprotein
- interacts with NFKB1/p105
- autophosphorylated
- longer form undergoes phosphorylation on Ser mainly, & the shorter form on both Ser & Thr
ATP + a protein <--> ADP + a phosphoprotein
Structure
- belongs to the protein kinase superfamily, STE Ser/Thr protein kinase family, MAP kinase kinase kinase subfamily
- contains 1 protein kinase domain
Compartment
Alternative initiation
- named isoforms=2
Expression
- expressed in several normal tissues & human tumor-derived cell lines
- 58 kD form is activated specifically during the S & G2/M phases of the cell cycle
More general terms
References
- ↑ Hunter T. Cooperation between oncogenes. Cell. 1991 Jan 25;64(2):249-70. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/1988147
- ↑ Lin X, Cunningham ET Jr, Mu Y, Geleziunas R, Greene WC. The proto-oncogene Cot kinase participates in CD3/CD28 induction of NF-kappaB acting through the NF-kappaB-inducing kinase and IkappaB kinases. Immunity. 1999 Feb;10(2):271-80. PMID: https://www.ncbi.nlm.nih.gov/pubmed/10072079
- ↑ UniProt http://www.uniprot.org/uniprot/P41279.html