RhoA signaling in phorbol ester-induced apoptosis.
Exposure of cells to phorbol ester activates protein kinase C (PKC) to induce apoptosis or differentiation, depending on the cellular context. In erythroblastic cell lines, TF-1 and D2, upregulation of the RhoA signaling promotes phorbol ester-induced apoptosis through activating Rho-associated kinase (ROCK)/phosphorylation of myosin light chain (MLC), thus generating membrane contraction force. As a result, cell adhesion is inhibited and death receptor-mediated death pathway is activated in these cells with a concurrent changes in nucleocytoplasmic signaling for protein trafficking. A microtubule-regulated GEF-H1, which is a specific RhoA activator, was identified to contribute to RhoA activation in these cells. Thus, a cytoskeleton-regulated RhoA signaling cooperates with PKC activation constitutes a cellular context to determine the cell fate in response to phorbol ester stimulation.
Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, No. 1, Section 1, Jen-Ai Road, Taipei, Taiwan, ROC. zfchang@ha.mc.ntu.edu.tw
Zee-Fen
ZF
Chang
Hsiao-Hui
HH
Lee
D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D006801:Humans; D010703:Phorbol Esters / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction; D020742:rhoA GTP-Binding Protein / Q000502:physiology*
D010703:Phorbol Esters; D011493:Protein Kinase C; D020742:rhoA GTP-Binding Protein