PMID- 10521487
OWN - NLM
STAT- MEDLINE
DCOM- 19991123
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 43
DP  - 1999 Oct 22
TI  - Heart 6-phosphofructo-2-kinase activation by insulin results from Ser-466 and
      Ser-483 phosphorylation and requires 3-phosphoinositide-dependent kinase-1, but
      not protein kinase B.
PG  - 30927-33
AB  - Previous studies have shown that (i) the insulin-induced activation of heart
      6-phosphofructo-2-kinase (PFK-2) is wortmannin-sensitive, but is insensitive to
      rapamycin, suggesting the involvement of phosphatidylinositol 3-kinase; and (ii) 
      protein kinase B (PKB) activates PFK-2 in vitro by phosphorylating Ser-466 and
      Ser-483. In this work, we have studied the effects of phosphorylation of these
      residues on PFK-2 activity by replacing each or both residues with glutamate.
      Mutation of Ser-466 increased the V(max) of PFK-2, whereas mutation of Ser-483
      decreased citrate inhibition. Mutation of both residues was required to decrease 
      the K(m) for fructose 6-phosphate. We also studied the insulin-induced activation
      of heart PFK-2 in transfection experiments performed in human embryonic kidney
      293 cells. Insulin activated transfected PFK-2 by phosphorylating Ser-466 and
      Ser-483. Kinase-dead (KD) PKB and KD 3-phosphoinositide-dependent kinase-1
      (PDK-1) cotransfectants acted as dominant negatives because both prevented the
      insulin-induced activation of PKB as well as the inactivation of
      glycogen-synthase kinase-3, an established substrate of PKB. However, the
      insulin-induced activation of PFK-2 was prevented only by KD PDK-1, but not by KD
      PKB. These results indicate that the insulin-induced activation of heart PFK-2 is
      mediated by a PDK-1-activated protein kinase other than PKB.
FAU - Bertrand, L
AU  - Bertrand L
AD  - Hormone and Metabolic Research Unit, Universite catholique de Louvain, Institute 
      of Cellular Pathology, Avenue Hippocrate, 75, B-1200 Brussels, Belgium.
FAU - Alessi, D R
AU  - Alessi DR
FAU - Deprez, J
AU  - Deprez J
FAU - Deak, M
AU  - Deak M
FAU - Viaene, E
AU  - Viaene E
FAU - Rider, M H
AU  - Rider MH
FAU - Hue, L
AU  - Hue L
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 (Insulin)
RN  - 0 (Peptide Fragments)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 17885-08-4 (Phosphoserine)
RN  - 452VLY9402 (Serine)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
RN  - EC 2.7.1.105 (Phosphofructokinase-2)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Amino Acid Sequence
MH  - Amino Acid Substitution
MH  - Animals
MH  - Cattle
MH  - Cell Line
MH  - Enzyme Activation
MH  - Humans
MH  - Insulin/*pharmacology
MH  - Kinetics
MH  - Mutagenesis, Site-Directed
MH  - Myocardium/*enzymology
MH  - Peptide Fragments/chemistry
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Phosphofructokinase-2
MH  - Phosphorylation
MH  - Phosphoserine/*metabolism
MH  - Phosphotransferases (Alcohol Group Acceptor)/chemistry/isolation &
      purification/*metabolism
MH  - *Protein-Serine-Threonine Kinases
MH  - Proto-Oncogene Proteins/metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Recombinant Proteins/chemistry/isolation & purification/metabolism
MH  - Serine
MH  - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
MH  - Transfection
EDAT- 1999/10/16 00:00
MHDA- 1999/10/16 00:01
CRDT- 1999/10/16 00:00
PHST- 1999/10/16 00:00 [pubmed]
PHST- 1999/10/16 00:01 [medline]
PHST- 1999/10/16 00:00 [entrez]
AID - 10.1074/jbc.274.43.30927 [doi]
AID - S0021-9258(19)51767-7 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Oct 22;274(43):30927-33. doi: 10.1074/jbc.274.43.30927.