Phorbol mimic

The phorbol esters are useful for studying the function of PKC since they mimic the stimulatory effects of DAG on the enzyme. These tumor-promoting plant products and their synthetic derivatives are able to penetrate intact cells. Many inferences regarding the intracellular actions of PKC are based on results of studies on whole-cell preparations with the phorbol esters. These substances, like DAG, may produce feedback inhibition of signal transduction at a number of metabolic levels. Results of experiments using phorbol esters in whole cells are thus often complex and must be interpreted cautiously. Notwithstanding this consideration, based upon... 

Gschwendt M, Furstenberger G, Rose-John S, Rogers M, Kittstein W, Pettit GR, Herald CL, Marks F (1988) Bryostatin 1, an activator of protein kinase C, mimics as well as inhibits biological effects of the phorbol ester TPA in vivo and in vitro. Carcinogenesis 9 555-562... 

Smith JB, Smith L, Pettit GR (1985) Bryostatins potent new mitogens that mimic phorbol ester tumor promoters. Biochem. Biophys Res Commun 132 939-945... 

Lead has similarities to calcium, one of the normal second messengers. Other substances can also stimulate PKC, such as phorbol esters and the fungal toxin funionism, which mimic diacylglycerol, another second messenger. 

CRF. Activation of protein kinase C by phorbol esters or synthetic diacylglycerols of CRF-stimulated cells mimics the synergistic action of vasopressin and CRF [48]. As mentioned above, this may be mediated by phosphorylation by protein kinase C of one of the regulatory components of CRF-stimulated adenylate cyclase [48]. 

Hunzicker-Dunn et al. [73] and Ezra and Salomon [74] suggested that the desensitization of the ovarian adenylate cyclase system by LH involves a phosphorylation reaction. The latter may alter the conformation of the receptor and/or Gs. If phosphorylation is the mechanism it may well be mediated by protein kinase C because phorbol esters, which are presumed to activate this enzyme, mimic LH induced desensitization in Leydig tumour cells [75,76]. There are, however, differences between LH- and phorbol ester induced desensitization [76], Cyclic AMP-dependent protein kinase is probably not involved because dibutyryl cyclic AMP does not mimic LH induced desensitization in Leydig cells [70]. 

Recall that phorbol esters mimic the action of DAG, the normal cell metabolite that activates protein kinase C (PKC). PKC initiates a phosphorylation cascade that results in the activation of numerous molecules involved in cell growth and division, including jun and fos, which then combine to form AP-1. AP-1 is a transcription factor whose presence promotes cell division. Its formation causes an affected cell to have a growth advantage over nearby cells. Because photbol esters are tumor promoters any exposure to them increases the risk that initiated cells may progress toward a cancerous state. 

Smith, J.B., L. Smith, and G.R. Pettit Bryostatins Potent, New Mitogens that Mimic Phorbol Ester Tumor Promoters. Biochem. Biophys. Res. Comm. 132, 939 (1985). 

Keck, G.E., Kraft, M.B., Truong, A.P., Li, W, Sanchez, C.C., Kedei, N Lewin, N.E., and Blumberg, P.M. (2008) Convergent assembly of highly potent analogues of bryostatin A via pyran armulation bryostatin look-alikes that mimic phorbol ester function. J. Am. Chem. Soc., 130, 6660-6661. 

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