FGR PROTOONCOGENE IS EXPRESSED DURING TERMINAL GRANULOCYTIC DIFFERENTIATION OF HUMAN PROMYELOCYTIC HL-60 CELLS

In order to elucidate the function of the c-fgr protein tyrosien kinas e, we have investigated the expression of c-fgr in the human promyeloc ytic cell line, HL60, during myeloid differentiation induced by dimeth ylsulfoxide (DMSO). The expression of c-fgr was preceded by growth arr est of DMSO-treated cells, as determined by [H-3]-thymidine incorporat ion and colony-forming ability, and it became detectable when cells co mmitted for terminal differentiation. The maximum expression was detec ted in the terminal stage of differentiation. The profile of tyrosine phosphorylation in cellular proteins was distinct among cells at vario us stages of the differentiation program. The 116 kd tyrosine-phosphor ylated protein detected in exponentially proliferating HL60 cells dimi nished during the course of the growth arrest and a distinct profile o f tyrosine phosphorylation (including 177 and 165 kd proteins) appeare d in cells undergoing terminal granulocytic differentiation. These fin dings implicate the involvement of p55(c-fgr) in the process of termin al granulocytic differentiation. However, the tyrosine kinase activity of p55(c-frg) expressed in differentiating HL60 cells was markedly in hibited by the tyrosine phosphatase inhibitor, sodium orthovanadate, s uggesting the presence of a mechanism involving tyrosine phosphorylati on that negatively regulates the kinase activity of p55(c-fgr).