Activation of PKC is required for arsenite-induced signal transduction.

Abstract

Trivalent arsenic (arsenite) is a human carcinogen. However, the molecular mechanism of arsenite-induced carcinogenesis is still not well understood. In this study, we found that arsenite induced translocation of PKCepsilon, PKCdelta, and PKCalpha from cytosol to membranes. Rottlerin, a selective inhibitor for PKCdelta, and safingol, a specific inhibitor for PKCalpha, both markedly inhibited arsenite-induced AP-1 activity. These inhibitory effects by rottlerin and safingol appeared to be dose dependent. Arsenite-induced phosphorylation of Erks was inhibited by rottlerin, while safingol inhibited arsenite-induced phosphorylation of JNKs and p38 kinases. Dominant negative mutant transfectant of PKCepsilon markedly blocked arsenite-induced AP-1 activity and the phosphorylation of Erks, JNKs, and p38 kinases. These data demonstrate that PKCdelta, PKCepsilon, and PKCalpha mediate arsenite-induced AP-1 activation in JB6 cells through different MAP kinase (Erks, JNKs, and p38 kinases) pathways.

Keywords

RottlerinArsenitep38 mitogen-activated protein kinasesKinasePhosphorylationSignal transductionProtein kinase CCell biologyCytosolMitogen-activated protein kinaseBiologyChemistryBiochemistryMolecular biologyProtein kinase AArsenicEnzyme

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Publication Info

Year: 2000
Type: article
Volume: 19
Issue: 3
Pages: 297-305
Citations: 47
Access: Closed

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APA Style

                            
                                    Nanyue Chen, 
                                
                                    Wei-Ya Ma, 
                                
                                    Chuanshu Huang
                                
                                et al.
                            
                            (2000). 
                            Activation of PKC is required for arsenite-induced signal transduction.. 
                            PubMed
                            , 19
                            (3)
                            , 297-305.