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 Ste2 0-like kinases (62-65% similar). MST1 is expressed ubiquitously, and t he MST1 protein is present in all human cell lines examined. Biochemic al 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 char acterization of the protein indicates MST1 activity increases approxim ately 3-4-fold upon treatment with PP2A, suggesting that MST1 is negat ively regulated by phosphorylation. MST1 activity decreases approximat ely 2-fold upon treatment with epidermal growth factor; however, overe xpression of MST1 does not affect extracellular signal-regulated kinas e-1 and -2 activation. MST1 is unaffected by heat shock or high osmola rity, indicating that it is not involved in the stress-activated or hi gh osmolarity glycerol signal transduction pathways. Thus MST1, althou gh homologous to a member of a yeast MAPK cascade, is not involved in the regulation of a known mammalian MAPK pathway and potentially regul ates a novel signaling cascade.