MOLECULAR-CLONING OF L-JAK, A JANUS FAMILY PROTEIN-TYROSINE KINASE EXPRESSED IN NATURAL-KILLER-CELLS AND ACTIVATED LEUKOCYTES

Protein-tyrosine kinases (PTKs) are critical enzymes for receptor-medi ated signaling in lymphocytes. Because natural killer (NK) cells are l arge granular lymphocytes with specialized effector function, we set o ut to identify PTKs preferentially expressed in these cells. One such PTK was identified and molecularly cloned. The predicted amino acid se quence shows that this kinase lacks SH2 or SH3 domains typical of src family kinases but has tandem nonidentical catalytic domains, indicati ng that it is a member of the Janus family of PTKs. Immunoprecipitatio n using antiserum generated against a peptide corresponding to the ded uced amino acid sequence of this gene revealed a kinase with a molecul ar weight of approximate to 125,000. The pattern of expression of this kinase contrasted sharply with that of other Janus kinases, which are ubiquitously expressed. The kinase described in the present study was found to be more limited in its expression; expression was found in N K cells and an NK-like cell line but not in resting T cells or in othe r tissues. In contrast, stimulated and transformed T cells expressed t he gene, suggesting a role in lymphoid activation. Because of its homo logy and tissue expression, we have tentatively termed this PTK gene L -JAK for leukocyte Janus kinase.