GM-CSF and phorbol esters modulate GM-CSF receptor expression by independent mechanisms

Maria F. Brizzi, Carlo Arduino, G. Carlo Avanzi, Federico Bussolino, Luigi Pegoraro

Research output: Contribution to journalArticlepeer-review

Abstract

Human granulocyte-macrophage colony-stimulating factor (GM-CSF) (0.1 nM) down-modulates its receptor in 1L-3/GM-CSF dependent M-07e cells, in KG-1 cells and normal granulocytes, whereas phorbol esters 12-O-tetradecanoylphorbol-13-acetate (TPA) (2 nM) down-modulates the GM-CSF receptor in M-07e cells and granulocytes but not in KG-1 cells. As data analysis shows by nonlinear regression, the decreased binding ability depends on a reduction of the binding sites with no significant change of their dissociation constant. To gain insight into the mechanisms involved in the GM-CSF receptor regulation, we investigated the role of protein kinase C (PKC). GM-CSF, unlike TPA, was unable to activate PKC in all the cells studied. Moreover, unlike TPA, GM-CSF was still able to down-modulate its receptor in cells where PKC was inhibited by 1-(5-isoquinolonesulphonyl)-2-methylpiperazine (H7) and staurosporine or in cells where PKC was exhausted by prolonged incubation with 1 μM TPA. Finally, the receptor re-expression rate was accelerated by protein kinases inhibitors. These results, taken together, indicate the presence of a PKC-dependent and -independent down-modulation mechanism and a negative role of the endogeneous protein kinases in GM-CSF receptor re-expression.

Original languageEnglish
Pages (from-to)24-34
Number of pages11
JournalJournal of Cellular Physiology
Volume148
Issue number1
Publication statusPublished - Jul 1991

ASJC Scopus subject areas

  • Cell Biology
  • Clinical Biochemistry
  • Physiology

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