Phorbol 12-myristate 13-acetate (PMA), a phorbol ester, is a dual SphK and protein kinase C (PKC) activator. IC50 & Target: EC50: 11.7 nM (PKC)^[1] In Vitro: In order to examine the role of PKC in p38MAPK phosphorylation, the cells are stimulated with the PKC activator, PMA (100 nM), which mimics the binding of DAG, the natural activator of PKC, to the C1 region of the PKCs. p38MAPK phosphorylation by PMA is observed in the two cell types similar to that observed by GnRH in αT3-1 cells, that is, a slow sustained activation (3.2-fold and 3.6-fold, respectively at 30 min). The paradoxical findings that PKCs activated by GnRH and PMA play a differential role in p38MAPK phosphorylation may be explained by differential localization of the PKCs. Basal, GnRH- and PMA- stimulation of p38MAPK phosphorylation in αT3-1 cells is mediated by Ca²⁺ influx via voltage-gated Ca²⁺ channels and Ca²⁺ mobilization, while in the differentiated LβT2 gonadotrope cells it is mediated only by Ca²⁺ mobilization^[2]. In Vivo: PMA is a PKC agonist, which reverses the damage induced by 5-hydroxydecanoic acid (5-HD). Thus, activation of the mitoKATP protected mitochondrial function in SOD and MDA via the PKC pathway^[3].