Translocation of protein kinase Cε and protein kinase Cδ to membrane is required for ultraviolet B-induced activation of mitogen-activated protein kinases and apoptosis

UV-induced signal transduction may be involved in tumor promotion and induction of apoptosis, The role of protein kinase C (PKC) in UVB-induced signal transduction is not well understood. This study showed that UVB markedly induced translocation of membrane-associated PKC epsilon and PKC delta, but not PKC alpha, from cytosol to membrane. Dominant negative mutant (DNM) PKC epsilon or PKC delta inhibited UVB-induced translocation of PKC epsilon and PKC delta, respectively, UVB-induced activation of extracellular signal-regulated protein kinases (Erks) and c-Jun NH2-terminal kinases (JNKs) was strongly inhibited by DNM PKC epsilon and PKC delta, whereas the DNM of PKC alpha was less effective on the UVB-induced phosphorylation of Erks and JNKs, Among the PKC inhibitors used only rottlerin, a selective inhibitor of PKC delta, markedly inhibited the UVB-induced activation of Erks and JNKs, but not p38 kinases, Safingol, a selective inhibitor for PKC alpha, did not show any inhibitory effect on UVB-induced mitogen-activated protein kinase activation. GF109203X is a stronger inhibitor of classical PKC than novel PKC, Lower concentrations of GF109203X (<10 mu M) had no effect on UVB-induced activation of Erks or JNKs, However, at higher concentrations (over 20 mu M), GF109203X inhibited UVB-induced activation of JNKs, Erks, and even p38 kinases. Meanwhile, rottlerin and GF109203X markedly inhibited UVB-induced apoptosis of JB6 cells, whereas safingol had little inhibitory effect. DNM-Erk2 cells and PD98059, a selective inhibitor for mitogen-activated protein kinase/extracellular signal-regulated kinase 1 that directly activates Erks, inhibited UVB-induced apoptosis. DNM-JNK1 cells also blocked UVB-induced apoptosis, whereas SB202190, a specific inhibitor for p38 kinases, did not produce the inhibitory effect. These data demonstrate that PKC delta and PKC epsilon, but not PKC alpha, mediate UVB-induced signal transduction and apoptosis in JB6 cells through activation of Erks and JNKs.