Association and activation of Btk and Tec tyrosine kinases by gp130, a signal transducer of the interleukin-6 family of cytokines.
Interleukin-6 (IL-6), leukemia inhibitory factor, oncostatin M, IL-11, and ciliary neurotrophic factor constitute the IL-6 family of cytokines and play important roles in hematopoiesis, immune response, and nervous system. The receptors for the IL-6 family of cytokines share gp130 through which signals are generated, although the cytoplasmic region of gp130 does not contain any catalytic domain. In this study we show that in addition to Jak family tyrosine kinase, the stimulation of gp130 by IL-6 plus soluble IL-6 receptor alpha induced the activation of Btk and Tec tyrosine kinases, whereas IL-3 and granulocyte colony-stimulating factor activated Tec but not Btk in a pro-B cell line. Furthermore, both Btk and Tec kinases were associated with gp130 without the ligand stimulation. Because Btk is a critical tyrosine kinase for B lymphopoiesis and Tec is considered to be involved in hematopoiesis, the results suggest the involvement of gp130-Btk-Tec signal pathway in early lymphohematopoiesis.
Matsuda
T
T
Division of Molecular Oncology, Osaka University Medical School, Japan.
Takahashi-Tezuka
M
M
Fukada
T
T
Okuyama
Y
Y
Fujitani
Y
Y
Tsukada
S
S
Mano
H
H
Hirai
H
H
Witte
O N
ON
Hirano
T
T
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D015703:Antigens, CD; D001402:B-Lymphocytes; D002460:Cell Line; D050822:Cytokine Receptor gp130; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006410:Hematopoiesis; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D010750:Phosphoproteins / Q000302:isolation & purification / Q000378:metabolism; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D018121:Receptors, Cytokine / Q000378:metabolism*; D018123:Receptors, Interleukin / Q000378:metabolism*; D016185:Receptors, Interleukin-3 / Q000378:metabolism; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction; D014162:Transfection; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
D015703:Antigens, CD; C494199:IL6ST protein, human; C494200:Il6st protein, mouse; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D010750:Phosphoproteins; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; D016185:Receptors, Interleukin-3; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins; D050822:Cytokine Receptor gp130; D016179:Granulocyte Colony-Stimulating Factor; D019000:Phosphotyrosine; D014443:Tyrosine; C089848:Tec protein-tyrosine kinase; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human