ACTIVATION OF FES TYROSINE KINASE BY GP130, AN INTERLEUKIN-6 FAMILY CYTOKINE SIGNAL TRANSDUCER, AND THEIR ASSOCIATION

gp130 is a signal-transducing subunit of receptors for the interleukin -6 (IL-6)-related cytokine subfamily including IL-6, leukemia inhibito ry factor, oncostatin M, IL-11, and ciliary neurotrophic factor, indic ating that gp130-mediated signals are involved in the immune response, hematopoiesis, inflammation, and endocrine and nervous system activit y. We previously showed that gp130 stimulation rapidly activates Jak, Btk, and Tec tyrosine kinases, all of which constitutively associate w ith gp130, To further elucidate intracellular signal transduction thro ugh gp130, we examined the possible involvement of another nonreceptor tyrosine kinase, p92(c-fes) (Fes). We showed that gp130 stimulation r apidly induced tyrosine phosphorylation of Fes and actually activated its kinase activity in hematopoietic lineage cells. Furthermore, Fes a ssociated with gp130 independently of ligand stimulation like Jak, Btk , and Tec tyrosine kinases. These results indicate that multiple nonre ceptor tyrosine kinases are involved in the gp130-mediated signal tran sduction pathway. Because both gp130 and Fes are expressed not only in hematopoietic lineage cells but also in heart and nerve cells, Fes ma y play a role in signal transduction through gp130 in these tissues.