Document Detail

Phosphatidylinositol 3-kinase is required for growth factor-induced amino acid uptake by vascular smooth muscle cells.
MedLine Citation:
PMID:  10479654     Owner:  NLM     Status:  MEDLINE    
Although accumulating evidence suggests that phosphatidylinositol 3-kinase (PI3K) is a common signaling molecule for growth factor-induced amino acid uptake by the cell, the role of PI3K in the uptake of different amino acids was not tested under the same conditions. In this study, we asked whether PI3K mediates platelet-derived growth factor (PDGF) -stimulated uptake of different amino acids that are taken up through 3 major amino acid transporters expressed in rat vascular smooth muscle cells and other cell types and whether PI3K mediates amino acid uptake stimulated with different growth factors and vasoactive substances. PDGF increased the uptake of [(3)H]leucine, [(3)H]proline, and [(3)H]arginine in a dose- and time-dependent fashion. Two different PI3K inhibitors, wortmannin (100 nmol/L) and LY294002 (10 micromol/L), completely inhibited the amino acid uptake stimulated by PDGF. Chinese hamster ovary cells expressing both PDGF receptor-beta and a dominant-negative PI3K did not increase their leucine uptake when stimulated with PDGF, whereas the same cells expressing only PDGF receptor-beta did. Transforming growth factor-beta, as well as insulin-like growth factor-I and angiotensin II, increased leucine uptake by vascular smooth muscle cells. Wortmannin and LY294002 inhibited this increase. We also found that transforming growth factor-beta stimulated PI3K activity and the phosphorylation of Akt, a downstream signaling molecule of PI3K. A similar effect of PI3K inhibitors on amino acid uptake was observed in Swiss 3T3 cells. We conclude that PI3K mediates the uptake of different amino acids by vascular smooth muscle cells and other cell types stimulated with a variety of growth factors, including transforming growth factor-beta. Our findings suggest that PI3K may play an important role in vascular pathophysiology by regulating amino acid uptake.
M Higaki; K Shimokado
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  19     ISSN:  1079-5642     ISO Abbreviation:  Arterioscler. Thromb. Vasc. Biol.     Publication Date:  1999 Sep 
Date Detail:
Created Date:  1999-10-07     Completed Date:  1999-10-07     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9505803     Medline TA:  Arterioscler Thromb Vasc Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2127-32     Citation Subset:  IM    
National Cardiovascular Center Research Institute, Osaka, Japan.
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MeSH Terms
1-Phosphatidylinositol 3-Kinase / genetics,  metabolism,  physiology*
Amino Acids / metabolism*
Angiotensin II / pharmacology
CHO Cells
Cells, Cultured
Genes, Dominant
Growth Substances / pharmacology*
Insulin-Like Growth Factor I / pharmacology
Leucine / pharmacokinetics
Muscle, Smooth, Vascular / cytology,  metabolism*
Platelet-Derived Growth Factor / pharmacology
Rats, Sprague-Dawley
Receptors, Platelet-Derived Growth Factor / metabolism
Recombinant Proteins / pharmacology
Transforming Growth Factor beta / pharmacology
Reg. No./Substance:
0/Amino Acids; 0/Growth Substances; 0/Platelet-Derived Growth Factor; 0/Recombinant Proteins; 0/Transforming Growth Factor beta; 0/platelet-derived growth factor BB; 11128-99-7/Angiotensin II; 61-90-5/Leucine; 67763-96-6/Insulin-Like Growth Factor I; EC 3-Kinase; EC, Platelet-Derived Growth Factor

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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