A novel nonreceptor tyrosine kinase, Srm: cloning and targeted disruption.
We have isolated a novel nonreceptor tyrosine kinase, Srm, that maps to the distal end of chromosome 2. It has SH2, SH2', and SH3 domains and a tyrosine residue for autophosphorylation in the kinase domain but lacks an N-terminal glycine for myristylation and a C-terminal tyrosine which, when phosphorylated, suppresses kinase activity. These are structural features of the recently identified Tec family of nonreceptor tyrosine kinases. The Srm N-terminal unique domain, however, lacks the structural characteristics of the Tec family kinases, and the sequence similarity is highest to Src in the SH region. The expression of two 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 constitutes a new family of nonreceptor tyrosine kinases that may be redundant in function.
Kohmura
N
N
Laboratory of Molecular Oncology, Tsukuba Life Science Center, Ibaraki, Japan.
Yagi
T
T
Tomooka
Y
Y
Oyanagi
M
M
Kominami
R
R
Takeda
N
N
Chiba
J
J
Ikawa
Y
Y
Aizawa
S
S
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004847:Epithelial Cells; D051379:Mice; D008815:Mice, Inbred Strains / Q000196:embryology / Q000235:genetics*; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009420:Nervous System / Q000166:cytology; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D013234:Stem Cells / Q000166:cytology; D019061:src-Family Kinases
D009419:Nerve Tissue Proteins; C089510:SRMS protein, human; D011505:Protein-Tyrosine Kinases; D019061:src-Family Kinases