Catalytic activity:ATP + a protein = ADP + a phosphoprotein. ,cofactor:Magnesium. ,enzyme regulation:Contains an N-terminal autoinhibitory domain. Activated by phosphorylation at Thr-838 , inhibited by phosphorylation at Ser-966 and Ser-1033. Binds to , and stabilizes MAP3K6 and is activated by MAP3K6 by phosphorylation on Thr-838. ,Function:Component of a protein kinase signal transduction cascade. Phosphorylates and activates MAP2K4 and MAP2K6 , which in turn activate the JNK and p38 MAP kinases , respectively. Overexpression induces apoptotic cell death. ,induction:By TNF-alpha. Inhibited by HIV-1 Nef. ,similarity:Belongs to the protein kinase superfamily. ,similarity:Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily. ,similarity:Contains 1 protein kinase domain. ,subunit:Homodimer when inactive. Binds both upstream activators and downstream substrates in multimolecular complexes. Associates with and inhibited by HIV-1 Nef. Interacts with DAB2IP and PPM1L. ,tissue specificity:Abundantly expressed in heart and pancreas. ,
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