Molecular cloning of lsk, a carboxyl-terminal src kinase (csk) related gene, expressed in leukocytes.
Regulation of the activity of src-family kinases is thought to occur, in part, through the phosphorylation of conserved carboxyl-terminal tyrosine residues. Although the src-family includes several molecules with tissue or cell-type restricted expression, the only kinase implicated in the regulatory phosphorylation of these enzymes is p50csk. Herein we report the molecular cloning of a tissue specific p50csk-related gene. Like p50csk, the deduced protein sequence of this novel cDNA includes a tyrosine kinase catalytic domain, SH2 and SH3 domains, a short amino terminus, and no autophosphorylation or carboxyl-terminal tyrosine residues. Additionally, neither this novel kinase nor p50csk contain the amino-terminal myristoylation site characteristic of the src-family. However, whereas csk is ubiquitously expressed, mRNA corresponding to this novel gene is expressed in brain, natural killer (NK) cells, and activated T cells but not in a variety of other tissues and cell lines. In agreement with the mRNA expression pattern, antiserum reactive with the predicted carboxyl-terminus of the cDNA recognizes a 57 kDa polypeptide in immunoblots of NK cells and PHA-activated T cells. Because of its limited expression and high homology to p50csk, we named this gene lsk; leukocyte carboxyl-terminal src kinase related gene. Identification of a molecule like lsk suggests the existence of tissue specific src-regulatory pathways that function in activated lymphocytes.
McVicar
D W
DW
Leukocyte Cell Biology Section, Inc./DynCorp, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702-1201.
Lal
B K
BK
Lloyd
A
A
Kawamura
M
M
Chen
Y Q
YQ
Zhang
X
X
Staples
J E
JE
Ortaldo
J R
JR
O'Shea
J J
JJ
D000595:Amino Acid Sequence; D001483:Base Sequence; D000081247:CSK Tyrosine-Protein Kinase; D002460:Cell Line; D003001:Cloning, Molecular; D018076:DNA, Complementary; D006801:Humans; D007694:Killer Cells, Natural / Q000201:enzymology* / Q000378:metabolism; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology; D019061:src-Family Kinases
D018076:DNA, Complementary; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; C085377:MATK protein, human; D016392:Proto-Oncogene Proteins pp60(c-src); D019061:src-Family Kinases; C000631346:CSK protein, human