Erythropoietin stimulates nuclear localization of diacylglycerol and protein kinase C beta II in B6SUt.EP cells.
Erythropoietin (EPO) is a hormone, as well as a hematopoietic growth factor, that specifically regulates the proliferation and differentiation of erythroid progenitor cells. Although the membrane-bound receptor for EPO has no intrinsic kinase activity, it triggers the activation of protein kinases via phospholipases A2, C, and D. A cascade of serine and threonine kinases, including Raf-1, MAP kinase and protein kinase C (PKC) is activated following tyrosine phosphorylation. In this study, we have examined whether changes in nuclear PKC and 1,2-diacylglycerol (DAG) are induced following EPO treatment of the murine target cell line, B6SUt.EP. Western blot analysis using isoform-specific antibodies demonstrated the presence of PKC beta II, but not PKC alpha, beta I, gamma, epsilon, delta, eta, or zeta in the nuclei of cells stimulated with EPO. The increase in nuclear beta II levels was accompanied by an immediate rise in DAG mass levels with both of the increases peaking by 1 min. These rapid increases in nuclear DAG and PKC beta II expression suggest a mechanism for EPO-induced changes in gene expression necessary for cell proliferation.
Mallia
C M
CM
Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112, USA.
Smith
M
M
Clejan
S
S
Beckman
B S
BS
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism*; D004921:Erythropoietin / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D008954:Models, Biological; D011493:Protein Kinase C / Q000378:metabolism*; D064546:Protein Kinase C beta; D011994:Recombinant Proteins; D015398:Signal Transduction; D013347:Subcellular Fractions / Q000378:metabolism
D004075:Diglycerides; D007527:Isoenzymes; D011994:Recombinant Proteins; D004921:Erythropoietin; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D017871:Calcium-Calmodulin-Dependent Protein Kinases