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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2009-2-2
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pubmed:abstractText |
The phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway is highly conserved throughout evolution and regulates cell size and survival and cell cycle progression. It regulates the latter by stimulating procession through G(1) and the G(1)/S phase transition. Entry into S phase requires an abundant supply of purine nucleotides, but the effect of the PI3K/Akt pathway on purine synthesis has not been studied. We now show that the PI3K/Akt cassette regulates both de novo and salvage purine nucleotide synthesis in insulin-responsive mouse mesenchymal cells. We found that serum and insulin stimulated de novo purine synthesis in serum-starved cells largely through PI3K/Akt signaling, and pharmacologic and genetic inhibition of PI3K/Akt reduced de novo synthesis by 75% in logarithmically growing cells. PI3K/Akt regulated early steps of de novo synthesis by modulating phosphoribosylpyrophosphate production by the non-oxidative pentose phosphate pathway and late steps by modulating activity of the bifunctional enzyme aminoimidazole-carboxamide ribonucleotide transformylase IMP cyclohydrolase, an enzyme not previously known to be regulated. The effects of PI3K/Akt on purine nucleotide salvage were likely through regulating phosphoribosylpyrophosphate availability. These studies define a new mechanism whereby the PI3K/Akt cassette functions as a master regulator of cellular metabolism and a key player in oncogenesis.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19068483-1002693,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19068483-10567431,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19068483-10579924,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19068483-10597272,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19068483-11138960,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19068483-11390360,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19068483-12501179,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19068483-12851486,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19068483-13906397,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19068483-14517300,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19068483-14561707,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19068483-15114530,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19068483-16027121,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19068483-16449529,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19068483-17604717,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19068483-17712357,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19068483-2581946,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19068483-3109390,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19068483-4077987,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19068483-4115637,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19068483-4337750,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19068483-4726295,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19068483-5665447,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19068483-5767308,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19068483-6171305,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19068483-6199353,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19068483-6248594,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19068483-6279630,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19068483-6699001,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19068483-7470484,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19068483-7737463,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19068483-8034608,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19068483-8106507,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19068483-8646809,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19068483-9331084,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19068483-942051,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19068483-9742206
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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/AKT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Akt1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/IMP cyclohydrolase,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Nucleotide Deaminases,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoribosylaminoimidazolecarboxam...,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Purine Nucleotides
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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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 |
6
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pubmed:volume |
284
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3521-8
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:19068483-Animals,
pubmed-meshheading:19068483-Cell Line,
pubmed-meshheading:19068483-Cell Transformation, Neoplastic,
pubmed-meshheading:19068483-Evolution, Molecular,
pubmed-meshheading:19068483-G1 Phase,
pubmed-meshheading:19068483-Humans,
pubmed-meshheading:19068483-Insulin,
pubmed-meshheading:19068483-Mice,
pubmed-meshheading:19068483-Mice, Mutant Strains,
pubmed-meshheading:19068483-Nucleotide Deaminases,
pubmed-meshheading:19068483-Pentose Phosphate Pathway,
pubmed-meshheading:19068483-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:19068483-Phosphoribosylaminoimidazolecarboxamide Formyltransferase,
pubmed-meshheading:19068483-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:19068483-Purine Nucleotides,
pubmed-meshheading:19068483-S Phase,
pubmed-meshheading:19068483-Signal Transduction
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pubmed:year |
2009
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pubmed:articleTitle |
The phosphatidylinositol 3-kinase/akt cassette regulates purine nucleotide synthesis.
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pubmed:affiliation |
Department of Medicine, University of California San Diego, La Jolla, California 92093, USA.
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pubmed:publicationType |
Journal Article
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