PMID- 10357815
OWN - NLM
STAT- MEDLINE
DCOM- 19990805
LR  - 20191210
IS  - 0261-4189 (Print)
IS  - 0261-4189 (Linking)
VI  - 18
IP  - 11
DP  - 1999 Jun 1
TI  - Serum and glucocorticoid-inducible kinase (SGK) is a target of the PI
      3-kinase-stimulated signaling pathway.
PG  - 3024-33
AB  - Serum and glucocorticoid-inducible kinase (SGK) is a novel member of the
      serine/threonine protein kinase family that is transcriptionally regulated. In
      this study, we have investigated the regulatory mechanisms that control SGK
      activity. We have established a peptide kinase assay for SGK and present evidence
      demonstrating that SGK is a component of the phosphoinositide 3 (PI 3)-kinase
      signaling pathway. Treatment of human embryo kidney 293 cells with insulin, IGF-1
      or pervanadate induced a 3- to 12-fold activation of ectopically expressed SGK.
      Activation was completely abolished by pretreatment of cells with the PI 3-kinase
      inhibitor, LY294002. Treatment of activated SGK with protein phosphatase 2A in
      vitro led to kinase inactivation. Consistent with the similarity of SGK to other 
      second-messenger regulated kinases, mutation of putative phosphorylation sites at
      Thr256 and Ser422 inhibited SGK activation. Cotransfection of PDK1 with SGK
      caused a 6-fold activation of SGK activity, whereas kinase-dead PDK1 caused no
      activation. GST-pulldown assays revealed a direct interaction between PDK1 and
      the catalytic domain of SGK. Treatment of rat mammary tumor cells with serum
      caused hyperphosphorylation of endogenous SGK, and promoted translocation to the 
      nucleus. Both hyperphosphorylation and nuclear translocation could be inhibited
      by wortmannin, but not by rapamycin.
FAU - Park, J
AU  - Park J
AD  - Friedrich Miescher-Institut, Maulbeerstrasse 66, CH-4056 Basel, Switzerland.
FAU - Leong, M L
AU  - Leong ML
FAU - Buse, P
AU  - Buse P
FAU - Maiyar, A C
AU  - Maiyar AC
FAU - Firestone, G L
AU  - Firestone GL
FAU - Hemmings, B A
AU  - Hemmings BA
LA  - eng
GR  - CA-71514/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (Androstadienes)
RN  - 0 (Blood Proteins)
RN  - 0 (Glucocorticoids)
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (Insulin)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (pervanadate)
RN  - 3WHH0066W5 (Vanadates)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - EC 2.7.11.1 (3-Phosphoinositide-Dependent Protein Kinases)
RN  - EC 2.7.11.1 (PDPK1 protein, human)
RN  - EC 2.7.11.1 (Pdpk1 protein, rat)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (serum-glucocorticoid regulated kinase)
RN  - EC 3.1.3.16 (Phosphoprotein Phosphatases)
RN  - EC 3.1.3.16 (Protein Phosphatase 2)
RN  - W36ZG6FT64 (Sirolimus)
RN  - XVA4O219QW (Wortmannin)
SB  - IM
MH  - 3-Phosphoinositide-Dependent Protein Kinases
MH  - Amino Acid Sequence
MH  - Androstadienes/pharmacology
MH  - Animals
MH  - Blood Proteins/pharmacology
MH  - Cell Line
MH  - Cell Nucleus/enzymology/metabolism
MH  - Enzyme Activation/drug effects
MH  - Glucocorticoids/pharmacology
MH  - Humans
MH  - Immediate-Early Proteins
MH  - Insulin/pharmacology
MH  - Insulin-Like Growth Factor I/pharmacology
MH  - Molecular Sequence Data
MH  - Mutation
MH  - *Nuclear Proteins
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Phosphoprotein Phosphatases/metabolism
MH  - Phosphorylation/drug effects
MH  - Precipitin Tests
MH  - Protein Binding
MH  - Protein Phosphatase 2
MH  - Protein-Serine-Threonine Kinases/genetics/*metabolism
MH  - Signal Transduction/*drug effects
MH  - Sirolimus/pharmacology
MH  - Substrate Specificity
MH  - Vanadates/pharmacology
MH  - Wortmannin
PMC - PMC1171384
EDAT- 1999/06/05 00:00
MHDA- 1999/06/05 00:01
CRDT- 1999/06/05 00:00
PHST- 1999/06/05 00:00 [pubmed]
PHST- 1999/06/05 00:01 [medline]
PHST- 1999/06/05 00:00 [entrez]
AID - 10.1093/emboj/18.11.3024 [doi]
PST - ppublish
SO  - EMBO J. 1999 Jun 1;18(11):3024-33. doi: 10.1093/emboj/18.11.3024.