PMID- 10597260
OWN - NLM
STAT- MEDLINE
DCOM- 20000104
LR  - 20181130
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 18
IP  - 47
DP  - 1999 Nov 11
TI  - Protein kinase C-alpha overexpression stimulates Akt activity and suppresses
      apoptosis induced by interleukin 3 withdrawal.
PG  - 6564-72
AB  - 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.
FAU - Li, W
AU  - Li W
AD  - Laboratory of Cellular and Molecular Biology, National Cancer Institute,
      Bethesda, Maryland, MD 20892, USA.
FAU - Zhang, J
AU  - Zhang J
FAU - Flechner, L
AU  - Flechner L
FAU - Hyun, T
AU  - Hyun T
FAU - Yam, A
AU  - Yam A
FAU - Franke, T F
AU  - Franke TF
FAU - Pierce, J H
AU  - Pierce JH
LA  - eng
PT  - Journal Article
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Androstadienes)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Interleukin-3)
RN  - 0 (Isoenzymes)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 452VLY9402 (Serine)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.13 (Protein Kinase C-alpha)
RN  - XVA4O219QW (Wortmannin)
SB  - IM
MH  - Androstadienes/pharmacology
MH  - *Apoptosis/drug effects
MH  - Cell Line
MH  - DNA Replication
MH  - Enzyme Inhibitors/pharmacology
MH  - Interleukin-3/administration & dosage/*pharmacology
MH  - Isoenzymes/genetics/*metabolism
MH  - Phosphorylation
MH  - Protein Kinase C/genetics/*metabolism
MH  - Protein Kinase C-alpha
MH  - *Protein-Serine-Threonine Kinases
MH  - Proto-Oncogene Proteins/chemistry/genetics/*metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Serine/metabolism
MH  - Transfection
MH  - Wortmannin
EDAT- 1999/12/22 00:00
MHDA- 1999/12/22 00:01
CRDT- 1999/12/22 00:00
PHST- 1999/12/22 00:00 [pubmed]
PHST- 1999/12/22 00:01 [medline]
PHST- 1999/12/22 00:00 [entrez]
AID - 10.1038/sj.onc.1203065 [doi]
PST - ppublish
SO  - Oncogene. 1999 Nov 11;18(47):6564-72. doi: 10.1038/sj.onc.1203065.