PMID- 7774014
OWN - NLM
STAT- MEDLINE
DCOM- 19950713
LR  - 20220408
IS  - 0092-8674 (Print)
IS  - 0092-8674 (Linking)
VI  - 81
IP  - 5
DP  - 1995 Jun 2
TI  - The protein kinase encoded by the Akt proto-oncogene is a target of the 
      PDGF-activated phosphatidylinositol 3-kinase.
PG  - 727-36
AB  - The serine/threonine protein kinase encoded by the Akt proto-oncogene is 
      catalytically inactive in serum-starved primary and immortalized fibroblasts. 
      Here we show that Akt and the Akt-related kinase AKT2 are activated by PDGF. The 
      activation was rapid and specific, and it was abrogated by mutations in the Akt 
      Pleckstrin homology (PH) domain. The Akt activation was also shown to depend on 
      PDGFR beta tyrosines Y740 and Y751, which bind phosphatidylinositol 3-kinase (PI 
      3-kinase) upon phosphorylation. Moreover, Akt activation was blocked by the PI 
      3-kinase-specific inhibitor wortmannin and the dominant inhibitory N17Ras. 
      Conversely, Akt activity was induced following the addition of 
      phosphatidylinositol-3-phosphate to Akt immunoprecipitates from serum-starved 
      cells in vitro. These results identify Akt as a novel target of PI 3-kinase and 
      suggest that the Akt PH domain may be a mediator of PI 3-kinase signaling.
FAU - Franke, T F
AU  - Franke TF
AD  - Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
FAU - Yang, S I
AU  - Yang SI
FAU - Chan, T O
AU  - Chan TO
FAU - Datta, K
AU  - Datta K
FAU - Kazlauskas, A
AU  - Kazlauskas A
FAU - Morrison, D K
AU  - Morrison DK
FAU - Kaplan, D R
AU  - Kaplan DR
FAU - Tsichlis, P N
AU  - Tsichlis PN
LA  - eng
GR  - CA-55063/CA/NCI NIH HHS/United States
GR  - R01-CA38047/CA/NCI NIH HHS/United States
GR  - R01-CA57436/CA/NCI NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cell
JT  - Cell
JID - 0413066
RN  - 0 (Androstadienes)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Oncogene Proteins)
RN  - 0 (Phosphatidylinositol 4,5-Diphosphate)
RN  - 0 (Phosphatidylinositol Phosphates)
RN  - 0 (Platelet-Derived Growth Factor)
RN  - 0 (Proto-Oncogene Proteins)
RN  - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
RN  - EC 2.7.10.1 (Receptors, Platelet-Derived Growth Factor)
RN  - EC 2.7.11.1 (Akt1 protein, rat)
RN  - EC 2.7.11.1 (Akt2 protein, mouse)
RN  - EC 2.7.11.1 (Akt2 protein, rat)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.6.5.2 (ras Proteins)
RN  - XVA4O219QW (Wortmannin)
SB  - IM
MH  - Androstadienes/pharmacology
MH  - Animals
MH  - Cells, Cultured
MH  - Enzyme Activation/drug effects
MH  - Enzyme Induction
MH  - Enzyme Inhibitors/pharmacology
MH  - *Gene Expression Regulation, Enzymologic
MH  - Mice
MH  - Models, Biological
MH  - Oncogene Proteins/drug effects/metabolism
MH  - Phosphatidylinositol 3-Kinases
MH  - Phosphatidylinositol 4,5-Diphosphate
MH  - Phosphatidylinositol Phosphates/pharmacology
MH  - Phosphotransferases (Alcohol Group Acceptor)/*metabolism
MH  - Platelet-Derived Growth Factor/*pharmacology
MH  - Protein Serine-Threonine Kinases/drug effects/metabolism
MH  - Proto-Oncogene Proteins/drug effects/*metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Proto-Oncogenes
MH  - Rats
MH  - Receptors, Platelet-Derived Growth Factor/metabolism
MH  - Sequence Homology, Amino Acid
MH  - *Signal Transduction
MH  - Wortmannin
MH  - ras Proteins/metabolism
EDAT- 1995/06/02 00:00
MHDA- 1995/06/02 00:01
CRDT- 1995/06/02 00:00
PHST- 1995/06/02 00:00 [pubmed]
PHST- 1995/06/02 00:01 [medline]
PHST- 1995/06/02 00:00 [entrez]
AID - 0092-8674(95)90534-0 [pii]
AID - 10.1016/0092-8674(95)90534-0 [doi]
PST - ppublish
SO  - Cell. 1995 Jun 2;81(5):727-36. doi: 10.1016/0092-8674(95)90534-0.