1728320

pubmed:Citation

1

The proto-oncogene c-myc has been identified as an early response gene for erythropoietin (Epo) in transformed murine erythroleukemia cells. Epo activation of c-myc in these cells requires protein kinase C. We now show the fidelity of this signaling pathway in normal erythroid cells isolated from the spleens of phenylhydrazine-treated mice. Mouse spleen cells rich in erythroid progenitors were washed free of endogenous Epo and then incubated in the absence of Epo. Subsequent addition of Epo for 1 hour led to a dramatic elevation of c-myc transcript. Addition of the protein synthesis inhibitor cycloheximide did not prevent the c-myc response, thus identifying c-myc as an Epo early response gene in normal cells. We used this c-myc response as a reporter for signals initiated by the Epo receptor. Using a series of inhibitors with known specificities and established rank-orders of potency for different kinases, we determined that the c-myc response to Epo was blocked with the following rank order: staurosporine much greater than H7 greater than sangivamycin greater than H8. This sequence is identical to that obtained using transformed cells and is diagnostic of a protein kinase C-dependent signal. Because direct activation of protein kinase by phorbol esters does not induce terminal differentiation of normal cells, the pathway to c-myc established by these studies must represent one part of a signal transduction mechanism.

eng

AIM

MEDLINE

0006-4971

Print

79

NLM

52-7

pubmed-meshheading:1728320-1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine, pubmed-meshheading:1728320-Alkaloids, pubmed-meshheading:1728320-Animals, pubmed-meshheading:1728320-Erythroid Precursor Cells, pubmed-meshheading:1728320-Erythropoietin, pubmed-meshheading:1728320-Gene Expression, pubmed-meshheading:1728320-Genes, myc, pubmed-meshheading:1728320-Isoquinolines, pubmed-meshheading:1728320-Mice, pubmed-meshheading:1728320-Mice, Inbred C57BL, pubmed-meshheading:1728320-Phenylhydrazines, pubmed-meshheading:1728320-Piperazines, pubmed-meshheading:1728320-Protein Kinase C, pubmed-meshheading:1728320-Pyrimidine Nucleosides, pubmed-meshheading:1728320-Signal Transduction, pubmed-meshheading:1728320-Spleen, pubmed-meshheading:1728320-Staurosporine, pubmed-meshheading:1728320-Transcription, Genetic

c-myc is an erythropoietin early response gene in normal erythroid cells: evidence for a protein kinase C-mediated signal.

Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.