Protein kinase C activity and hexamethylenebisacetamide-induced erythroleukemia cell differentiation.

E. Melloni, S. Pontremoli, M. Michetti, O. Sacco, A. G. Cakiroglu, J. F. Jackson, R. A. Rifkind, P. A. Marks

Research output: Contribution to journalArticle

Abstract

Hexamethylenebisacetamide (HMBA) is a potent inducer of murine erythroleukemia (MEL) cell differentiation. The mechanism of action of HMBA is not known. In this study we provide evidence that protein kinase C has a role in inducer-mediated MEL cell differentiation: (i) HMBA induces the formation of a soluble, proteolytically activated form of protein kinase C that is catalytically active in the absence of Ca2+ and phospholipid; (ii) the protease inhibitor leupeptin blocks formation of this activated form of the kinase and inhibits HMBA-induced MEL cell hemoglobin accumulation; (iii) phorbol 12-myristate 13-acetate (PMA) inhibits HMBA-induced MEL differentiation and causes depletion of total protein kinase C activity; (iv) MEL cells depleted in protein kinase C activity by culture with PMA are resistant to induction by HMBA; (v) upon removal of PMA, restoration of MEL cell sensitivity to HMBA is correlated with reaccumulation of protein kinase C activity; and (vi) MEL cells grown to density arrest are both depleted of protein kinase C activity and resistant to HMBA. Together, these results suggest that HMBA-mediated MEL cell differentiation involves a protein kinase C-related mechanism and the proteolytically activated form of the kinase, which does not require Ca2+ or phospholipid for its catalytic activity.

Original languageEnglish
Pages (from-to)5282-5286
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume84
Issue number15
Publication statusPublished - Aug 1987

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Leukemia, Erythroblastic, Acute
Protein Kinase C
Cell Differentiation
Acetates
Phospholipids
Phosphotransferases
Protease Inhibitors
Hemoglobins

ASJC Scopus subject areas

  • General
  • Genetics

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Protein kinase C activity and hexamethylenebisacetamide-induced erythroleukemia cell differentiation. / Melloni, E.; Pontremoli, S.; Michetti, M.; Sacco, O.; Cakiroglu, A. G.; Jackson, J. F.; Rifkind, R. A.; Marks, P. A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 84, No. 15, 08.1987, p. 5282-5286.

Research output: Contribution to journalArticle

Melloni, E, Pontremoli, S, Michetti, M, Sacco, O, Cakiroglu, AG, Jackson, JF, Rifkind, RA & Marks, PA 1987, 'Protein kinase C activity and hexamethylenebisacetamide-induced erythroleukemia cell differentiation.', Proceedings of the National Academy of Sciences of the United States of America, vol. 84, no. 15, pp. 5282-5286.
Melloni, E. ; Pontremoli, S. ; Michetti, M. ; Sacco, O. ; Cakiroglu, A. G. ; Jackson, J. F. ; Rifkind, R. A. ; Marks, P. A. / Protein kinase C activity and hexamethylenebisacetamide-induced erythroleukemia cell differentiation. In: Proceedings of the National Academy of Sciences of the United States of America. 1987 ; Vol. 84, No. 15. pp. 5282-5286.
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