Association of p72 tyrosine kinase with Stat factors and its activation by interleukin-3, interleukin-6, and granulocyte colony-stimulating factor.
Hematopoietic cytokines, including interleukin-3 (IL-3), IL-6, and granulocyte colony-stimulating factor (G-CSF), induce the proliferation, differentiation, and activation of hematopoietic lineage cells. These cytokines activate the Jak/Stat-mediated signal transduction pathway that is important in the biologic activities of these cytokines. In this study, we showed that hematopoietic cytokines, such as IL-3, IL-6, and G-CSF, all induced tyrosine-phosphorylation of Stat family proteins and Stat-associated 150-kD and 72-kD molecules in hematopoietic lineage cell lines. Furthermore, we showed that the 72-kD molecule had tyrosine kinase activity. The tyrosine kinase activity of the 72-kD molecule was enhanced by the stimulation through an IL-6 signal transducer, gp130, that was shared among the receptors for the IL-6-related cytokine subfamily, such as leukemia inhibitory factor, oncostatin M, IL-11, and ciliary neurotrophic factor. Because 72-kD tyrosine kinase was distinct from Syk, Tec, and Btk and coimmunoprecipitated with anti-Stat antiserum, we termed it Stat-associated 72-kD tyrosine kinase (p72sak). p72sak may directly activate Stat family proteins or other signal transducing molecules for IL-3, G-CSF, and the IL-6-related cytokine subfamily.
Matsuda
T
T
Division of Molecular Oncology, Osaka University Medical School, Japan.
Hirano
T
T
D000818:Animals; D002460:Cell Line; D004789:Enzyme Activation; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D011817:Rabbits; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*
D007377:Interleukin-3; D015850:Interleukin-6; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D016179:Granulocyte Colony-Stimulating Factor; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; C507924:JAK2 protein, human; D053613:Janus Kinase 1; D053614:Janus Kinase 2