title: 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.
authors.affiliation: Division of Hematologic Malignancies, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: T J
authors.initials: TJ
authors.lastname: Ernst
authors.forename: K E
authors.initials: KE
authors.lastname: Slattery
authors.forename: J D
authors.initials: JD
authors.lastname: Griffin
mesh_terms: D000595:Amino Acid Sequence; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D016374:Oncogene Proteins v-abl / Q000378:metabolism*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051578:Proto-Oncogene Proteins c-fes; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D016374:Oncogene Proteins v-abl; D011518:Proto-Oncogene Proteins; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; C496645:FES protein, human; D016044:Fusion Proteins, bcr-abl; D051578:Proto-Oncogene Proteins c-fes