A NOVEL NONRECEPTOR TYROSINE KINASE, SRM - CLONING AND TARGETED DISRUPTION

We have isolated a novel nonreceptor tyrosine kinase, Srm, that maps t o the distal end of chromosome 2. It has SH2, SH2', and SH3 domains an d a tyrosine residue for autophosphorylation in the kinase domain but lacks an N-terminal glycine for myristylation and a C-terminal tyrosin e which, when phosphorylated, suppresses kinase activity. These are st ructural features of the recently identified Tec family of nonreceptor tyrosine kinases. The Srm N-terminal unique domain, however, lacks th e structural characteristics of the Tec family kinases, and the sequen ce similarity is highest to Src in the SH region. The expression of tw o transcripts is rather ubiquitous and changes according to tissue and developmental stage. Mutant mice were generated by gene targeting in embryonic stem cells but displayed no apparent phenotype as in mutant mice expressing Src family kinases. These results suggest that Srm con stitutes a new family of nonreceptor tyrosine kinases that may be redu ndant in function.