Two protein kinase C activators, bryostatin-1 and phorbol-12-myristate-13-acetate, have different effects on haemopoietic cell proliferation and differentiation.
Primary B lymphocytes can be induced to proliferate and certain haemopoietic cell lines such as HL60 and U937 can be induced to differentiate by the addition of phorbol esters, which have been shown to activate protein kinase C. Several non-phorbol esters, such as the bryostatins, have also been shown to bind to and activate protein kinase C. Although bryostatin-1 and 12-O-tetradecanoylphorbol-13-acetate (TPA) compete for and activate protein kinase C to the same degree and with similar kinetics and also induce similar levels of expression of the CD23 cell-surface antigen, bryostatin-1 is a weak mitogen for B lymphocytes and fails to induce the differentiation of both HL60 and U937 cells. Such an outcome suggests that these two activators have different binding properties for the enzyme that have a physiological consequence which may be useful for analysing the role that protein kinase C plays in both differentiation and proliferation. Analysis of competition assays between bryostatin-1 and TPA leads us to put forward a model where protein kinase C is required to be constantly reactivated and recycled during proliferation and differentiation which can be accomplished by TPA but not by bryostatin, although we cannot exclude the differential activation of some of the sub-species of the kinase by the two agonists.
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Institute of Molecular and Cell Biology, National University of Singapore.
Guy
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GR
D001402:B-Lymphocytes / Q000187:drug effects; D054713:Bryostatins; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D007783:Lactones / Q000494:pharmacology*; D018942:Macrolides; D010703:Phorbol Esters / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D017455:Receptors, IgE / Q000096:biosynthesis; D013997:Time Factors; D014407:Tumor Cells, Cultured
D054713:Bryostatins; D007783:Lactones; D018942:Macrolides; D010703:Phorbol Esters; D017455:Receptors, IgE; C046785:bryostatin 1; D011493:Protein Kinase C