Identification of interleukin-2 receptor-associated tyrosine kinase p116 as novel leukocyte-specific Janus kinase.
Janus tyrosine kinase (JAK) has recently been linked to signal transduction by cytokine receptors of the hematopoietin family. We have recently described a 116-kDa tyrosine kinase (p116) present in interleukin-2 (IL-2) receptor complexes in human YT cells that showed functional characteristics of a JAK kinase. These included receptor association, rapid and transient tyrosine phosphorylation kinetics in response to ligand, and in vitro autophosphorylating tyrosine kinase activity (Kirken, R. A., Rui, H., Evans, G. A., and Farrar, W. L. (1993) J. Biol. Chem. 268, 22765-22770). Here we extend these observations by demonstrating structural homologies between IL-2-modulated p116 and prolactin-modulated JAK2 in the rat T cell line Nb2. These include similar net charge as determined by nonequilibrium pH gradient electrofocusing and related primary structure based upon phosphopeptide mapping of V8 protease-digested hyperphosphorylated proteins. This putative JAK kinase underwent marked tyrosine phosphorylation in response to IL-2, IL-4, and IL-7, lymphoid growth factors that use the common IL-2 receptor gamma-chain, but not in response to prolactin. Furthermore, polyclonal antisera to JAK1, JAK2, or tyrosine kinase 2 did not recognize either rat or human p116. However, we identified the IL-2-modulated p116 as the recently cloned novel leukocyte Janus kinase, L-JAK, using an antiserum to a peptide corresponding to the COOH terminus of human L-JAK.
Kirken
R A
RA
Cytokine Molecular Mechanisms Section, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702.
Rui
H
H
Malabarba
M G
MG
Farrar
W L
WL
D000818:Animals; D002460:Cell Line; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D015851:Interleukin-7 / Q000494:pharmacology; D007526:Isoelectric Point; D053614:Janus Kinase 2; D053616:Janus Kinase 3; D007962:Leukocytes / Q000201:enzymology*; D008970:Molecular Weight; D010449:Peptide Mapping; D010750:Phosphoproteins / Q000737:chemistry / Q000276:immunology; D019000:Phosphotyrosine; D011388:Prolactin / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D007376:Interleukin-2; D015851:Interleukin-7; C507936:Jak3 protein, rat; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D015375:Receptors, Interleukin-2; D015847:Interleukin-4; D019000:Phosphotyrosine; D014443:Tyrosine; D011388:Prolactin; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; C507924:JAK2 protein, human; C507933:JAK3 protein, human; C507927:Jak2 protein, rat; D053614:Janus Kinase 2; D053616:Janus Kinase 3