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 inhibitory factor, oncostatin M, IL-11, and ciliary neurotrophic factor, indicating that gp130-mediated signals are involved in the immune response, hematopoiesis, inflammation, and endocrine and nervous system activity. We previously showed that gp130 stimulation rapidly activates Jak, Btk, and Tec tyrosine kinases, all of which constitutively associate with gp130. To further elucidate intracellular signal transduction through gp130, we examined the possible involvement of another nonreceptor tyrosine kinase, p92c-fes (Fes). We showed that gp130 stimulation rapidly induced tyrosine phosphorylation of Fes and actually activated its kinase activity in hematopoietic lineage cells. Furthermore, Fes associated with gp130 independently of ligand stimulation like Jak, Btk, and Tec tyrosine kinases. These results indicate that multiple nonreceptor tyrosine kinases are involved in the gp130-mediated signal transduction pathway. Because both gp130 and Fes are expressed not only in hematopoietic lineage cells but also in heart and nerve cells, Fes may play a role in signal transduction through gp130 in these tissues.
Matsuda
T
T
Division of Molecular Oncology, Osaka University Medical School, Japan.
Fukada
T
T
Takahashi-Tezuka
M
M
Okuyama
Y
Y
Fujitani
Y
Y
Hanazono
Y
Y
Hirai
H
H
Hirano
T
T
D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D001402:B-Lymphocytes; D002460:Cell Line; D050822:Cytokine Receptor gp130; D004789:Enzyme Activation; D006801:Humans; D015151:Immunoblotting; D015850:Interleukin-6 / Q000494:pharmacology*; D007700:Kinetics; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000302:isolation & purification / Q000378:metabolism*; D051379:Mice; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000302:isolation & purification / Q000378:metabolism*; D051578:Proto-Oncogene Proteins c-fes; D011519:Proto-Oncogenes; D018123:Receptors, Interleukin / Q000302:isolation & purification / Q000502:physiology*; D019947:Receptors, Interleukin-6; D015398:Signal Transduction; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C494199:IL6ST protein, human; C494200:Il6st protein, mouse; D015850:Interleukin-6; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6; D050822:Cytokine Receptor gp130; D019000:Phosphotyrosine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; C496645:FES protein, human; C496646:Fes protein, mouse; D051578:Proto-Oncogene Proteins c-fes