Rapid protein tyrosine phosphorylation selectively induced in murine responsive ELM-I-1 cells by erythropoietin.
We investigated whether protein tyrosine phosphorylation was induced by erythropoietin (Epo) in two murine Epo-responsive cell lines (ELM-I-1, which proliferates autonomously and is induced to differentiate by Epo, and DA-1ER, which grows in a manner dependent on Epo or interleukin-3 (IL-3) without differentiation). In ELM-I-1, Epo induced the tyrosine phosphorylation of a protein of about 80-85 kDa (py80) which appeared in the Triton-X soluble fraction of the cell lysate in a time- and concentration-dependent manner. Maximal levels of phosphorylation were obtained within 5-10 min at Epo concentrations above 0.1 U/ml. IL-3 is known to promote the proliferation of this cell line, but it did not induce py80 phosphorylation. In DA-1ER, tyrosine phosphorylation of py80 was not induced by either Epo or IL-3. These findings suggest that there are multiple pathways of Epo signaling and that one of them could be via tyrosine kinase activation. Furthermore, it is possible that the tyrosine phosphorylation of py80 is involved in the pathway leading only to erythroid differentiation but not to cellular proliferation.
Sawada
T
T
Second Department of Internal Medicine, Kumamoto University Medical School, Japan.
Tsuda
H
H
Kawakita
M
M
Takatsuki
K
K
D000818:Animals; D002460:Cell Line; D004790:Enzyme Induction / Q000187:drug effects; D004921:Erythropoietin / Q000494:pharmacology*; D051379:Mice; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019908:Proto-Oncogene Proteins c-raf; D011994:Recombinant Proteins / Q000494:pharmacology
D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D004921:Erythropoietin; D011505:Protein-Tyrosine Kinases; D019908:Proto-Oncogene Proteins c-raf