PMID- 10660304
OWN - NLM
STAT- MEDLINE
DCOM- 20000320
LR  - 20190728
IS  - 0960-9822 (Print)
IS  - 0960-9822 (Linking)
VI  - 10
IP  - 1
DP  - 2000 Jan 13
TI  - Serine phosphorylation and maximal activation of STAT3 during CNTF signaling is
      mediated by the rapamycin target mTOR.
PG  - 47-50
AB  - Neuropoletic cytokines such as ciliary neurotrophic factor (CNTF) can activate
      multiple signaling pathways in parallel, including those involving Janus kinase
      (JAK)-signal transducers and activators of transcription (STATs),
      mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI
      3-kinase) and mammalian target of rapamydn (mTOR)-p70 S6 kinase . Crosstalk
      occurs between these pathways, because studies have shown that STAT3 requires
      phosphorylation on tyrosine and serine residues by independent protein kinase
      activities for maximal activation of target gene transcription. Members of the
      JAK/Tyk family of tyrosine kinases mediate phosphorylation of STAT3 at Tyr705
      during CNTF signaling; however, the kinase responsible for phosphorylation at
      STAT3 Tyr727 appears to depend on both the extracellular stimulus and the
      cellular context. Here we investigate the kinase activity responsible for
      phosphorylation of STAT3 on Ser727 in CNTF-stimulated neuroblastoma cells. We
      found that CNTF-induced phosphorylation of Ser727 was inhibited by the mTOR
      inhibitor rapamycin, but not by inhibitors of MAPK and protein kinase C (PKC)
      activation. A STAT3 peptide was efficiently phosphorylated on Ser727 in a
      CNTF-dependent manner by mTOR, but not by a kinase-inactive mTOR mutant or by p70
      S6 kinase. In agreement with these biochemical studies, rapamycin treatment of
      cells transfected with a STAT-responsive promoter reporter decreased activation
      of the reporter to the same degree as a STAT3 Ser727Ala mutant The ability of
      mTOR to contribute to activation of STAT3 extends the function of mTOR in
      mammalian cells to include transcriptional regulation.
FAU - Yokogami, K
AU  - Yokogami K
AD  - Molecular Neuro-Oncology, Neurosurgical Service, Massachusetts General Hospital
      and Harvard Medical School, Boston 02129, USA.
FAU - Wakisaka, S
AU  - Wakisaka S
FAU - Avruch, J
AU  - Avruch J
FAU - Reeves, S A
AU  - Reeves SA
LA  - eng
GR  - R01 NS35996/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Curr Biol
JT  - Current biology : CB
JID - 9107782
RN  - 0 (Ciliary Neurotrophic Factor)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Peptide Fragments)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - 0 (Trans-Activators)
RN  - 17885-08-4 (Phosphoserine)
RN  - 452VLY9402 (Serine)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.1.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Cell Line
MH  - Ciliary Neurotrophic Factor/*pharmacology
MH  - DNA-Binding Proteins/*metabolism
MH  - Humans
MH  - MAP Kinase Signaling System
MH  - Peptide Fragments/pharmacology
MH  - Phosphorylation
MH  - Phosphoserine/*metabolism
MH  - Phosphotransferases (Alcohol Group Acceptor)/antagonists & inhibitors/drug
      effects/*physiology
MH  - *Protein Kinases
MH  - Protein Processing, Post-Translational/*drug effects
MH  - Recombinant Fusion Proteins/metabolism
MH  - Ribosomal Protein S6 Kinases/metabolism
MH  - STAT3 Transcription Factor
MH  - Serine/*metabolism
MH  - Signal Transduction/*drug effects
MH  - Sirolimus/*pharmacology
MH  - TOR Serine-Threonine Kinases
MH  - Trans-Activators/*metabolism
EDAT- 2000/02/05 09:00
MHDA- 2000/03/25 09:00
CRDT- 2000/02/05 09:00
PHST- 2000/02/05 09:00 [pubmed]
PHST- 2000/03/25 09:00 [medline]
PHST- 2000/02/05 09:00 [entrez]
AID - S0960-9822(99)00268-7 [pii]
AID - 10.1016/s0960-9822(99)00268-7 [doi]
PST - ppublish
SO  - Curr Biol. 2000 Jan 13;10(1):47-50. doi: 10.1016/s0960-9822(99)00268-7.