Proliferative action of erythropoietin is associated with rapid protein tyrosine phosphorylation in responsive B6SUt.EP cells.
Erythropoietin is a prime regulator of the growth and terminal differentiation of erythroid blood cells. However, little is understood concerning its molecular mechanism of action. Presently it is shown in the responsive, factor-dependent murine cell line B6SUt.EP that erythropoietin induces the tyrosine phosphorylation of six plasma membrane-associated proteins in a time- and concentration-dependent fashion (i.e. phosphoproteins PY153, PY140, PY100, PY93, PY74, and PY54). Among these, PY153 was prominent. For all proteins, maximal levels of phosphorylation were induced within 3-7 min at low factor concentrations (100-500 pM). These findings establish tyrosine kinase activation as a novel candidate pathway of erythropoietin-induced proliferation. In addition, the tyrosine phosphorylation of six proteins with identical Mr, as well as a Mr 104,000 protein, was induced in B6SUt.EP cells by interleukin 3. In contrast, no induced tyrosine phosphorylation was detectable in the erythropoietin-responsive, leukemic erythroid cell line. Rauscher Red 1, yet proteins of Mr 153,000 and 54,000 were shown to be phosphorylated constitutively at relative levels greater than those observed in B6SUt.EP cells. A possible role for these phosphoproteins in hematopoietic cell transformation is considered.
Quelle
F W
FW
Department of Molecular and Cell Biology, Pennsylvania State University, University Park 16802.
Wojchowski
D M
DM
D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002999:Clone Cells; D004921:Erythropoietin / Q000378:metabolism / Q000494:pharmacology*; D007377:Interleukin-3 / Q000494:pharmacology; D007700:Kinetics; D008565:Membrane Proteins / Q000302:isolation & purification / Q000378:metabolism*; D051379:Mice; D010750:Phosphoproteins / Q000302:isolation & purification; D014443:Tyrosine
D007377:Interleukin-3; D008565:Membrane Proteins; D010750:Phosphoproteins; D004921:Erythropoietin; D014443:Tyrosine