p210Bcr/Abl and p160v-Abl induce an increase in the tyrosine phosphorylation of p93c-Fes.

Abstract

Chronic myelogenous leukemia is caused by a reciprocal chromosomal translocation of human chromosomes 9 and 22. The resulting fusion protein, p210Bcr/Abl, has enhanced tyrosine kinase activity compared with the normal cellular homologue, p145c-Abl. Expression of this chimeric protein in hematopoietic cell lines results in a rapid progression to growth factor independence and increased tyrosine phosphorylation of a number of unidentified cellular proteins. In this study, we show that the phosphorylation state of the hematopoietically restricted tyrosine kinase, p93c-Fes, is increased. Increased phosphorylation of p93c-Fes was detected in p210Bcr/Abl(+) human leukemic cell lines, in primary leukemic cells from patients with chronic myelogenous leukemia, and in myeloid cell lines expressing p210Bcr/Abl after transfection. Furthermore, p93c-Fes phosphorylation was increased by p210Bcr/Abl even when coexpressed in NIH 3T3 fibroblasts. v-abl expression was also found to increase the tyrosine phosphorylation of p93c-Fes. This increased phosphorylation was found to be accompanied by an increase in the ability of p93c-Fes to phosphorylate exogenous substrates. p93c-Fes could contribute to the transforming activity of the abl oncogenes.