IDENTIFICATION AND INITIAL CHARACTERIZATION OF MSLK, A MURINE MEMBER OF THE STE20 FAMILY OF KINASES

Protein kinases play a major role in the regulation of cellular growth . We isolated a murine cDNA encoding a novel serine/threonine kinase ( referred to as mSLK) ubiquituously expressed during all stages of muri ne development and in all adult tissues examined. The cDNA codes for a 1233-amino-acid polypeptide characterized by an N-terminal catalytic domain and a large C-terminal region of unknown function. The sequence of the catalytic domain places mSLK in the STE20 family of cytoplasmi c kinases. The noncatalytic domain does not show significant homology to any known protein. mSLK expressed in either COS7 cells or in bacter ia was shown to contain kinase activity. The N-terminal fragment of mS LK was able to autophosphorylate on serine and threonine residues, pho sphorylate threonine residues on a C-terminal fragment of the molecule , and phosphorylate exogenous substrates myelin basic protein and hist one III in vitro. Furthermore, autophosphorylation of the catalytic do main was enhanced in the presence of the C-terminal fragment, which su ggests a possible regulatory role for the C-terminal region of mSLK. A genomic clone of mSLK was isolated and used for fluorescence in situ hybridization locating the mSLK gene on band D2 of mouse chromosome 19 . (C) 1998 Academic Press.