title: The PKCdelta -Abl complex communicates ER stress to the mitochondria - an essential step in subsequent apoptosis.
abstract: Conditions that compromise protein folding in the endoplasmic reticulum trigger the unfolded protein response (UPR), which either restores proper protein folding or results in cellular demise through apoptosis. In this study, we found that, in response to ER stress in vivo and in vitro, PKCdelta translocates to the ER where it binds to the tyrosine kinase Abl. Tyrosine phosphorylation and kinase activity of PKCdelta are required for PKCdelta binding to Abl in the ER. Moreover, we found that inhibition of PKCdelta by the PKCdelta-specific peptide inhibitor deltaV1-1 or by silencing of PKCdelta reduces ER-stress-induced JNK activation and inhibits ER-stress-mediated apoptosis. Furthermore, the inhibitor of PKCdelta kinase activity rottlerin blocks the translocation of the PKCdelta-Abl complex from the ER to the mitochondria and confers protection against apoptosis. Thus, PKCdelta communicates ER stress to the mitochondria by binding to ER-localized Abl. The PKCdelta-Abl complex then translocates to the mitochondria, communicating ER stress to this organelle, thereby, triggering apoptosis.
authors.affiliation: Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Qi
authors.forename: Daria
authors.initials: D
authors.lastname: Mochly-Rosen
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000201:enzymology*; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D021381:Protein Transport; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism
chemical_list: D014443:Tyrosine; D016315:Proto-Oncogene Proteins c-abl; D051745:Protein Kinase C-delta