ASSOCIATION AND ACTIVATION OF BTK AND TEC TYROSINE KINASES BY GP130, A SIGNAL TRANSDUCER OF THE INTERLEUKIN-6 FAMILY OF CYTOKINES

Interleukin-8 (IL-6), leukemia inhibitory factor, oncostatin M, IL-11, and ciliary neurotrophic factor constitute the IL-6 family of cytokin es and play important roles in hematopoiesis, immune response, and ner vous system. The receptors for the IL-6 family of cytokines share gp13 0 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 gp 130 by IL-6 plus soluble IL-6 receptor cu induced the activation of Bt k and Tec tyrosine kinases, whereas IL-3 and granulocyte colony-stimul ating factor activated Tec but not Btk in a pro-B cell line. Furthermo re, both Btk and Tec kinases were associated with gp130 without the li gand stimulation. Because Btk is a critical tyrosine kinase for B lymp hopoiesis and Tec is considered to be involved in hematopoiesis. the r esults suggest the involvement of gp130-Btk-Tec signal pathway in earl y lymphohematopoiesis. (C) 1995 by The American Society of Hematology.