Rapid activation by erythropoietin of protein kinase C in nuclei of erythroid progenitor cells.
The glycoprotein hormone erythropoietin (Ep) regulates the proliferation and differentiation of erythroid progenitor cells by a signal transduction system which is not well understood. It has recently been reported that prolactin, a mitogen and trophic hormone for liver, will activate a nuclear protein kinase C in hepatocytes. As similarities exist in the actions of Ep and prolactin in their target cells, we tested the hypothesis that Ep could activate protein kinase C in nuclei isolated from erythroid progenitor cells. In a pure population of such nuclei, Ep induced a rapid, time- and dose-dependent increase in phosphorylation of endogenous nuclear substrate which could be blocked by inhibitors of protein kinase C or by antibody to Ep. Other known activators of protein kinase C were also effective in this system. These findings show that Ep may exert its effects by a novel signalling pathway, the activation of a nuclear protein kinase C.
Mason-Garcia
M
M
Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana.
Weill
C L
CL
Beckman
B S
BS
D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D015672:Erythroid Precursor Cells / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D004921:Erythropoietin / Q000008:administration & dosage / Q000494:pharmacology*; D005333:Fetus; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D051379:Mice; D011388:Prolactin / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D015398:Signal Transduction
D004921:Erythropoietin; D011388:Prolactin; D011493:Protein Kinase C