AN EPIDERMAL GROWTH-FACTOR RECEPTOR JAK2 TYROSINE KINASE DOMAIN CHIMERA INDUCES TYROSINE PHOSPHORYLATION OF STAT5 AND TRANSDUCES A GROWTH SIGNAL IN HEMATOPOIETIC-CELLS

The Jak family of tyrosine kinases and the Stat family of transcriptio n factors have been implicated in transducing signals from the hematop oietic growth factor receptors. To explore the role played by a member of the Jak family, Jak2, in hematopoietic cell growth signaling, we c onstructed a chimeric cDNA coding for the Jak2 tyrosine kinase domain linked to the extracellular and transmembrane regions of the epidermal growth factor (EGF) receptor (EGFR) and expressed the chimera in an i nterleukin (IL)-3-dependent cell line, 32D. When deprived of IL-3, EGF prevented apoptosis of the transfected cells, induced dose dependent proliferation, and supported long-term growth. EGF stimulation of the transfectants induced dose-dependent tyrosine phosphorylation of the E GFR/Jak2 chimera and Stat5, which correlated with the EGF dose depende nce of cell proliferation. On the other hand, EGF did not induce tyros ine phosphorylation of other factors implicated in cytokine receptor s ignaling, including the IL-3 receptor beta subunit, Jak kinases, Stat proteins other than Stat5, Shc, Syp, and mitogen-activated protein kin ases. These results suggest that the activation of Jak2 may be suffici ent for transducing a growth signal in hematopoietic cells by activati ng the Stat5 pathway or previously unidentified signaling pathways. In addition, because EGF induces homodimerization of the EGFR to activat e its tyrosine kinase activity, the present study, which shows EGF-dep endent activation of the EGFR/Jak2 chimera, implies that Jak2 may also become activated by homodimerization.