Cloning and characterization of a human protein kinase with homology to Ste20.
A human protein kinase (termed MST1) has been cloned and characterized. The MST1 catalytic domain is most homologous to Ste20 and other Ste20-like kinases (62-65% similar). MST1 is expressed ubiquitously, and the MST1 protein is present in all human cell lines examined. Biochemical characterization of MST1 catalytic activity demonstrates that it is a serine/threonine kinase, and that it can phosphorylate an exogenous substrate as well as itself in an in vitro kinase assay. Further characterization of the protein indicates MST1 activity increases approximately 3-4-fold upon treatment with PP2A, suggesting that MST1 is negatively regulated by phosphorylation. MST1 activity decreases approximately 2-fold upon treatment with epidermal growth factor; however, overexpression of MST1 does not affect extracellular signal-regulated kinase-1 and -2 activation. MST1 is unaffected by heat shock or high osmolarity, indicating that it is not involved in the stress-activated or high osmolarity glycerol signal transduction pathways. Thus MST1, although homologous to a member of a yeast MAPK cascade, is not involved in the regulation of a known mammalian MAPK pathway and potentially regulates a novel signaling cascade.
Creasy
C L
CL
Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
Chernoff
J
J
D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D015152:Blotting, Northern; D015153:Blotting, Western; D002460:Cell Line; D003001:Cloning, Molecular; D017931:DNA Primers; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000737:chemistry; D006358:Hot Temperature; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007700:Kinetics; D020930:MAP Kinase Kinase Kinases; D008969:Molecular Sequence Data; D010766:Phosphorylation; D010957:Plasmids; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D000099317:Hippo Kinases
D017931:DNA Primers; D019204:GTP-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D020930:MAP Kinase Kinase Kinases; D017346:Protein Serine-Threonine Kinases; D017027:Protein Tyrosine Phosphatases; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; C095566:STK4 protein, human; D000099317:Hippo Kinases; C078754:STE20 protein, S cerevisiae