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-mediated signaling in lymphocytes. Because natural killer (NK) cells are large granular lymphocytes with specialized effector function, we set out to identify PTKs preferentially expressed in these cells. One such PTK was identified and molecularly cloned. The predicted amino acid sequence shows that this kinase lacks SH2 or SH3 domains typical of src family kinases but has tandem nonidentical catalytic domains, indicating that it is a member of the Janus family of PTKs. Immunoprecipitation using antiserum generated against a peptide corresponding to the deduced amino acid sequence of this gene revealed a kinase with a molecular weight of approximately 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 NK cells and an NK-like cell line but not in resting T cells or in other tissues. In contrast, stimulated and transformed T cells expressed the gene, suggesting a role in lymphoid activation. Because of its homology and tissue expression, we have tentatively termed this PTK gene L-JAK for leukocyte Janus kinase.
Leukocyte Cell Biology Section, Program Resources, Inc./DynCorp, National Cancer Institute, Frederick, MD 21702-1201.
M
M
Kawamura
D W
DW
McVicar
J A
JA
Johnston
T B
TB
Blake
Y Q
YQ
Chen
B K
BK
Lal
A R
AR
Lloyd
D J
DJ
Kelvin
J E
JE
Staples
J R
JR
Ortaldo
J J
JJ
O'Shea
D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D017931:DNA Primers; D015870:Gene Expression; D015723:Gene Library; D006801:Humans; D053616:Janus Kinase 3; D007694:Killer Cells, Natural / Q000201:enzymology*; D007962:Leukocytes / Q000201:enzymology* / Q000502:physiology; D008213:Lymphocyte Activation; D008297:Male; D008969:Molecular Sequence Data; D008970:Molecular Weight; D005810:Multigene Family; D009928:Organ Specificity; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000097:blood; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology
D017931:DNA Primers; D011505:Protein-Tyrosine Kinases; C507933:JAK3 protein, human; D053616:Janus Kinase 3