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This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Porfiri, E. Articles by Wickremasinghe, R. G. Search for Related Content PubMed PubMed Citation Articles by Porfiri, E. Articles by Wickremasinghe, R. G. Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Retinoic acid-induced granulocytic differentiation of HL60 human promyelocytic leukemia cells is preceded by downregulation of autonomous generation of inositol lipid-derived second messengers E Porfiri, AV Hoffbrand and RG Wickremasinghe Department of Haematology, Royal Free Hospital School of Medicine, London, UK. Inositol phosphates (InsPs) and diacyglycerol (DAG) are second messengers derived via the breakdown of inositol phospholipids, and which play important signalling roles in the regulation of proliferation of some cell types. We have studied the operation of this pathway during the early stages of retionic acid (RA)-induced granulocytic differentiation of HL60 myeloid leukemia cells. The autonomous breakdown of inositol lipids that occurred in HL60 cells labeled with [3H] inositol was completely abolished following 48 hours of RA treatment. The rate of influx of 45Ca2+ was also significantly decreased at 48 hours, consistent with the role of inositol lipid- derived second messengers in regulating Ca2+ entry into cells. The downregulation of inositol lipid metabolism clearly preceded the onset of reduced proliferation induced by RA treatment, and was therefore not a consequence of decreased cell growth. The generation of InsPs in RA- treated cells was reactivated by the fluoroaluminate ion, a direct activator of guanine nucleotide-binding protein(s) (G proteins) that regulate the inositol lipid signalling pathway. Subtle alterations to a regulatory mechanism may therefore mediate the RA-induced downregulation of this pathway. The data are consistent with the hypothesis that the autonomous generation of inositol lipid-derived second messengers may contribute to the continuous proliferation of HL60 cells, and that the RA-induced downregulation of this pathway may, in turn, play a role in signalling the cessation of proliferation that preceedes granulocytic differentiation. Volume 78, Issue 4, pp. 1069-1077, 08/15/1991 Copyright © 1991 by The American Society of Hematology CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. Katagiri, K. K. Yokoyama, T. Yamamoto, S. Omura, S. Irie, and T. Katagiri Lyn and Fgr Protein-tyrosine Kinases Prevent Apoptosis during Retinoic Acid-induced Granulocytic Differentiation of HL-60 Cells J. Biol. Chem., May 10, 1996; 271(19): 11557 - 11562. [Abstract] [Full Text] [PDF]

	Copyright © 1991 by American Society of Hematology         Online ISSN: 1528-0020