title: Protein kinase C-alpha overexpression stimulates Akt activity and suppresses apoptosis induced by interleukin 3 withdrawal.
abstract: To investigate the role of protein kinase C (PKC) in apoptotic signaling induced by cytokine withdrawal, we expressed PKC-alpha, -delta and -epsilon individually in the 32D myeloid progenitor cells. The parental and PKC-delta- and PKC-epsilon-transfected 32D cells underwent apoptosis within 24 h in the absence of interleukin 3. In contrast, expression of PKC-alpha inhibited the onset of apoptosis as determined by genomic DNA fragmentation and flow cytometric analysis. Correlating with the inhibition of apoptosis, PKC-alpha transfectants exhibited increased activity of the endogenous Akt serine/threonine kinase. Furthermore, PKC-alpha, but not PKC-delta or -epsilon, specifically activated overexpressed Akt. PKC-alpha-induced Akt activity was partially dependent on phosphoinositol 3' kinase (PI 3'K) since a PI 3'K inhibitor was able to suppress PKC-alpha-induced Akt activation. Both basal and interleukin 3-stimulated phosphorylation of Akt on serine 473 was enhanced in the PKC-alpha and Akt contransfectants. Coexpression of wild type Akt and PKC-alpha resulted in greater suppression of apoptosis than PKC-alpha expression alone. Together, our results demonstrate that suppression of apoptosis by PKC-alpha correlates with its ability of activating endogenous Akt. Furthermore, activation of overexpressed Akt by PKC-alpha is consistent with their synergistic effect on suppressing apoptosis, providing the strong evidence of cross talk between Akt and PKC-alpha.
authors.affiliation: Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, Maryland, MD 20892, USA.
authors.forename: W
authors.initials: W
authors.lastname: Li
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: L
authors.initials: L
authors.lastname: Flechner
authors.forename: T
authors.initials: T
authors.lastname: Hyun
authors.forename: A
authors.initials: A
authors.lastname: Yam
authors.forename: T F
authors.initials: TF
authors.lastname: Franke
authors.forename: J H
authors.initials: JH
authors.lastname: Pierce
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D004261:DNA Replication; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007377:Interleukin-3 / Q000008:administration & dosage / Q000494:pharmacology*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D051571:Protein Kinase C-alpha; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D012694:Serine / Q000378:metabolism; D014162:Transfection; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D004791:Enzyme Inhibitors; D007377:Interleukin-3; D007527:Isoenzymes; D011518:Proto-Oncogene Proteins; D012694:Serine; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D000077191:Wortmannin