STK10: Human Serine Threonine kinase 10
PDB Code: 2J7T
STK10 is a member of the STE20 family of serine/threonine kinases and the human homolog of the murine kinase LOK, a serine/threonine kinase highly expressed in lymphocytes. STK10 is closely related to the polo-like kinase kinase SLK and has been shown to associate with Plk1 and phosphorylate it in vitro.
STK10 knockout mice do not exhibit any obvious histopathologic abnormalities and showed normal distribution of B cells, T cells and their precursors in the bone marrow, thymus, spleen and lymph nodes as well as normal lymphocytes development.
STK10 has also been shown to play a role in modifying TcR/CD28 signals for activation of cytokine transcription and it is potentially involved in the regulation of LFA-1-mediated lymphocyte adhesion. STK10 has been found to be over-expressed in a number of tumor cells and a heterozygous somatic missense mutation (K277E) within the kinase domain has been found in human testicular germ-cell tumors.
STK10 has been co-crystallized with the cell-permeable pyrrole indolinone SU11274 ( (3Z)-N- (3-Chlorophenyl)- 3-((3,5-dimethyl- 4-((4-methylpiperazin -1-yl)carbonyl)-1H- pyrrol-2-yl)methylene) -N-methyl-2-oxo -2,3-dihydro-1H- indole-5-sulfonamide) which has been described as a potent inhibitor of Met kinase activity (IC50= 20 nM). SU11274 has been shown to inhibit HGF/SF-stimulated cellular signaling and Met-mediated tumorigenesis in various cancer cell lines.
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