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 ty rosine residues. Although the src-family includes several molecules wi th tissue or cell-type restricted expression, the only kinase implicat ed in the regulatory phosphorylation of these enzymes is p50(csk). Her ein we report the molecular cloning of a tissue specific p50(csk)-rela ted gene. Like p50(csk), the deduced protein sequence of this novel cD NA 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 p50(cs k) contain the amino-terminal myristoylation site characteristic of th e src-family. However, whereas csk is ubiquitously expressed, mRNA cor responding to this novel gene is expressed in brain, natural killer (N K) cells, and activated T cells but not in a variety of other tissues and cell lines. In agreement with the mRNA expression pattern, antiser um reactive with the predicted carboxyl-terminus of the cDNA recognize s a 57 kDa polypeptide in immunoblots of NK cells and PHA-activated T cells, Because of its limited expression and high homology to p50(csk) , we named this gene lsk; leukocyte carboxyl-terminal src kinase relat ed gene. Identification of a molecule like lsk suggests the existence of tissue specific src-regulatory pathways that function in activated lymphocytes.