Phorbol 12-myristate 13-acetate (PMA) is a phorbol ester that is commonly used to activate certain types of protein kinase C (PKC), including group A (α, βI, βII, γ) and group B (δ, ε, η, θ) isoforms.1 Phorbol esters, including PMA, are structurally analogous to diacylglycerol and activate PKC isoforms by associating with their C1 domains.2 Through PKC, PMA also activates certain MAP kinase pathways.3 Prolonged treatment of cells with PMA at high concentrations results in the downregulation of total PKC activity and is tumorigenic, whereas lower concentrations may be protective.4,5 In addition, PMA promotes hematopoietic differentiation.6,7 The aqueous solubility of PMA is about 10-fold better than that of phorbol-12,13-dibutyrate, indicating that PMA is preferable in cell-based studies. |
1 Blumberg, P.M. Protein kinase C as the receptor for the phorbol ester tumor promoters: Sixth Rhoads Memorial Award Lecture. Cancer Res 481-8 (1988). 2 Hurley, J.H., Newton, A.C., Parker, P.J., et al. Taxonomy and function of C1 protein kinase C homology domains. Protein Sci 6 477-480 (1997). 3 Seger, R., and Krebs, E.G. The MAPK signaling cascade. FASEB J 9 726-735 (1995). 4 Matthies, H.J.G., Palfrey, H.C., Hirning, L.D., et al. Down regulation of protein kinase C in neuronal cells: Effects on neurotransmitter release. J Neurosci 7(4) 1198-1206 (1987). 5 Nelson, T.J., and Alkon, D.L. Neuroprotective versus tumorigenic protein kinase C activators. Trends Biochem Sci 34(3) 136-145 (2009). 6 Clemens, M.J., Trayner, I., and Menaya, J. The role of protein kinase C isoenzymes in the regulation of cell proliferation and differentiation. J Cell Sci 103 881-887 (1992). 7 Smithgall, T.E. Signal transduction pathways regulating hematopoietic differentiation. Pharmacol Rev 50(1) (1998). |
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