CONVERGENCE OF SIGNALING BY INTERLEUKIN-3, GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR, AND MAST-CELL GROWTH-FACTOR ON JAK2 TYROSINE KINASE

Mast cell growth factor (MGF) (also called stem cell factor) synergize s with several lymphokines, including interleukin-3 (IL-3) and granulo cyte-macrophage colony-stimulating factor (GM CSF), to promote prolife ration and differentiation of certain hemopoietic progenitor cells. Al though similar patterns of tyrosine-phosphorylated proteins characteri ze cells stimulated by MGF, IL-3, and GM-CSF, only the MGF receptor is a tyrosine kinase, and the heterodimeric receptors for IL-3 and GM-CS F share a common beta subunit that is devoid of enzymatic activity. He re we show that signaling pathways utilized by all three cytokines inc lude the cytoplasmic tyrosine kinase JAK2. Analysis of several factor- dependent myeloid cell lines indicated that JAK2 is physically associa ted with the common beta subunit and with MGF receptor (c-Kit) even pr ior to ligand binding. However, each of the ligands induced elevated t yrosine phosphorylation of JAK2 and a consequent increase in its catal ytic activity. These results demonstrate for the first time the conver gence within the same myeloid cells of signaling pathways originating in two distinct lymphokine receptors and a tyrosine kinase receptor on activation of a cytoplasmic tyrosine kinase.