REQUIREMENT OF SRC KINASE LYN FOR INDUCTION OF DNA-SYNTHESIS BY GRANULOCYTE-COLONY-STIMULATING FACTOR

Treatment of cells with granulocyte colony-stimulating factor (G-CSF) leads to tyrosine phosphorylation of cellular proteins, G-CSF stimulat es both the activation of protein tyrosine kinases Lyn, Jak1, and Jak2 and the association of these enzymes with the G-CSF receptor, Wild-ty pe, lyn-deficient, and syk-deficient chicken B lymphocyte cell lines w ere transfected with the human G-CSF receptor, and stable transfectant s were studied, G-CSF-dependent tyrosyl phosphorylation of Jak1 and Ja k2 occurred in all three cell lines, Wild-type and syk-deficient trans fectants responded to G-CSF in a dose-responsive fashion with increase d thymidine incorporation, but none of the clones of lyn-deficient tra nsfectants did, Ectopic expression of Lyn, but not that of c-Src, in t he lyn-deficient cells restored their mitogenic responsiveness to G-CS F, Ectopic expression in wild-type cells of the kinase inactive form o f Lyn, but not of the kinase-inactive form of Jak2, inhibited thymidin e incorporation in response to G-CSF. These studies show that the abse nce of Lyn results in the loss of mitogenic signaling in the G-CSF sig naling pathway and that activation of Jak1 or Jak2 is not sufficient t o cause mitogenesis.