Protein kinase phorbol ester-stimulated responses

IP3 acts as the second messenger for Ca2+ mobilisation from the endoplasmic reticulum while DAG stimulates the Ca2+ sensitive protein kinase C (which modulates EGF receptor) and activates the plasma membrane Na+/H+ exchange carrier. In this function DAG is mimicked by phorbol esters which have a tumour promoting function. The effect of stimulating Na+/H+ exchange is to increase the intracellular pH and K+ concentration, conditions which are necessary to induce or maintain the proliferative response in quiescent cells (Rozengurt, 1986 Wakelam, 1989). 

In addition to protein kinase C enzymes, cells contain other receptors for phorbol esters and diacylglycerol. In mammals, proteins named a- and /1-chimaerins have been identified that lack protein kinase activity and bind phorbol esters and diacylglycerol with high affinity. Therefore, not all biological responses elicited by phorbol ester treatment can be attributed to protein kinase C stimulation (review Ron and Kaza-nietz, 1999). 

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