PMID- 10617634
OWN - NLM
STAT- MEDLINE
DCOM- 20000131
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 275
IP  - 1
DP  - 2000 Jan 7
TI  - Akt protein kinase inhibits Rac1-GTP binding through phosphorylation at serine 71
      of Rac1.
PG  - 423-8
AB  - A putative Akt kinase phosphorylation site ((64)ydRIRplSYp(73)) was found in
      Rac1/CDC42 and Rho family proteins (RhoA, RhoB, RhoC, and RhoG). Phosphorylation 
      of Rac1 by Akt kinase was assayed with recombinant Rac1 protein and the
      fluorescein-labeled Rac1 peptide. It was shown that the Rac1 peptide and the
      recombinant protein were phosphorylated by the activated recombinant Akt kinase
      and the lysate of SK-MEL28 cells, a human melanoma cell line. The phosphorylation
      of Rac1 inhibited its GTP-binding activity without any significant change in
      GTPase activity. Both the GTP-binding and GTPase activities of Rac1 S71A protein 
      (with the serine residue to be phosphorylated replaced with alanine) were
      abolished regardless of the treatment of Akt kinase. Akt kinase activity and Rac1
      peptide phosphorylation were down-regulated by the treatment of SK-MEL28 cells
      with wortmannin or LY294002 (a phosphoinositide 3-kinase inhibitor), but JNK/SAPK
      kinase activity was up-regulated. Thus, the results suggest that Akt kinase of
      the phosphoinositide 3-kinase signal transduction pathway phosphorylates serine
      71 of Rac1 as one of its authentic substrates and modulates the Rac1 signal
      transduction pathway through phosphorylation.
FAU - Kwon, T
AU  - Kwon T
AD  - Clinical Research Center, Samsung Biomedical Research Institute, Seoul 135-230,
      Republic of Korea.
FAU - Kwon, D Y
AU  - Kwon DY
FAU - Chun, J
AU  - Chun J
FAU - Kim, J H
AU  - Kim JH
FAU - Kang, S S
AU  - Kang SS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Androstadienes)
RN  - 0 (Chromones)
RN  - 0 (Morpholines)
RN  - 0 (Oligopeptides)
RN  - 0 (Peptide Fragments)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN  - 86-01-1 (Guanosine Triphosphate)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.6.5.2 (rac1 GTP-Binding Protein)
RN  - XVA4O219QW (Wortmannin)
SB  - IM
MH  - Androstadienes/pharmacology
MH  - Chromones/pharmacology
MH  - Guanosine Triphosphate/*metabolism
MH  - Mitogen-Activated Protein Kinases
MH  - Morpholines/pharmacology
MH  - Oligopeptides/metabolism
MH  - Peptide Fragments/metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphorylation
MH  - Protein Kinases/*metabolism
MH  - *Protein-Serine-Threonine Kinases
MH  - Proto-Oncogene Proteins/*metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Signal Transduction
MH  - Wortmannin
MH  - rac1 GTP-Binding Protein/*metabolism
EDAT- 2000/01/05 00:00
MHDA- 2000/01/05 00:01
CRDT- 2000/01/05 00:00
PHST- 2000/01/05 00:00 [pubmed]
PHST- 2000/01/05 00:01 [medline]
PHST- 2000/01/05 00:00 [entrez]
AID - 10.1074/jbc.275.1.423 [doi]
AID - S0021-9258(19)52881-2 [pii]
PST - ppublish
SO  - J Biol Chem. 2000 Jan 7;275(1):423-8. doi: 10.1074/jbc.275.1.423.