Involvement of phosphatidylinositol 3-kinase in the mediation of erythropoietin-induced activation of p70S6k.
We have previously shown that, in HCD-57 cells, erythropoietin (EPO) induces a biphasic activation of the ribosomal S6 kinase p70S6k, an enzyme playing a key role in the regulation of cell cycle progression. Here we present evidence that p70S6k is activated through both phosphatidylinositol (PI) 3-kinase-dependent and independent pathways: whereas the early phase of EPO-dependent stimulation of p70S6k activity was strongly suppressed by the potent PI 3-kinase inhibitor wortmannin, late phase was much less affected. The dose-dependent inhibition of cell growth by wortmannin indicates an important role of PI 3-kinase in the mediation of EPO-induced cell proliferation. Furthermore, our data suggest that the EPO-receptor-associated tyrosine kinase JAK2 is not essentially involved in the mediation of EPO-induced p70S6k activation.
Jaster
R
R
Institute of Medical Biochemistry, Medical Faculty of the University Rostock, Germany.
Bittorf
T
T
Brock
J
J
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002455:Cell Division; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004921:Erythropoietin / Q000494:pharmacology*; D053614:Janus Kinase 2; D004915:Leukemia, Erythroblastic, Acute; D051379:Mice; D016376:Oligonucleotides, Antisense; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology; D011518:Proto-Oncogene Proteins; D017467:Receptors, Erythropoietin / Q000502:physiology; D019893:Ribosomal Protein S6 Kinases; D015398:Signal Transduction / Q000502:physiology*; D014407:Tumor Cells, Cultured; D000077191:Wortmannin
D000730:Androstadienes; D004791:Enzyme Inhibitors; D004921:Erythropoietin; D053614:Janus Kinase 2; D016376:Oligonucleotides, Antisense; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D017467:Receptors, Erythropoietin; D019893:Ribosomal Protein S6 Kinases; D000077191:Wortmannin; C507926:Jak2 protein, mouse