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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
43
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pubmed:dateCreated |
1999-11-23
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pubmed:abstractText |
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.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphofructokinase-2,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoserine,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphotransferases (Alcohol Group...,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Serine
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
22
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pubmed:volume |
274
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
30927-33
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:10521487-Amino Acid Sequence,
pubmed-meshheading:10521487-Amino Acid Substitution,
pubmed-meshheading:10521487-Animals,
pubmed-meshheading:10521487-Cattle,
pubmed-meshheading:10521487-Cell Line,
pubmed-meshheading:10521487-Enzyme Activation,
pubmed-meshheading:10521487-Humans,
pubmed-meshheading:10521487-Insulin,
pubmed-meshheading:10521487-Kinetics,
pubmed-meshheading:10521487-Mutagenesis, Site-Directed,
pubmed-meshheading:10521487-Myocardium,
pubmed-meshheading:10521487-Peptide Fragments,
pubmed-meshheading:10521487-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:10521487-Phosphofructokinase-2,
pubmed-meshheading:10521487-Phosphorylation,
pubmed-meshheading:10521487-Phosphoserine,
pubmed-meshheading:10521487-Phosphotransferases (Alcohol Group Acceptor),
pubmed-meshheading:10521487-Protein-Serine-Threonine Kinases,
pubmed-meshheading:10521487-Proto-Oncogene Proteins,
pubmed-meshheading:10521487-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:10521487-Recombinant Proteins,
pubmed-meshheading:10521487-Serine,
pubmed-meshheading:10521487-Spectrometry, Mass, Matrix-Assisted Laser...,
pubmed-meshheading:10521487-Transfection
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pubmed:year |
1999
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pubmed:articleTitle |
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.
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pubmed:affiliation |
Hormone and Metabolic Research Unit, Université catholique de Louvain, Institute of Cellular Pathology, Avenue Hippocrate, 75, B-1200 Brussels, Belgium.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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