© 1999 American Heart Association, Inc.
Vascular Biology |
Phosphatidylinositol 3-Kinase Is Required for Growth Factor–Induced Amino Acid Uptake by Vascular Smooth Muscle Cells
From the National Cardiovascular Center Research Institute, Osaka, Japan.
Correspondence to Kentaro Shimokado, MD, National Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan. E-mail kshimoka{at}res.ncvc.go.jp
Abstract—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 [3H]leucine, [3H]proline, and [3H]arginine in a dose- and time-dependent fashion. Two different PI3K inhibitors, wortmannin (100 nmol/L) and LY294002 (10 µmol/L), completely inhibited the amino acid uptake stimulated by PDGF. Chinese hamster ovary cells expressing both PDGF receptor-ß and a dominant-negative PI3K did not increase their leucine uptake when stimulated with PDGF, whereas the same cells expressing only PDGF receptor-ß did. Transforming growth factor-ß, 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-ß 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-ß. Our findings suggest that PI3K may play an important role in vascular pathophysiology by regulating amino acid uptake.
Key Words: phosphatidylinositol 3-kinase • amino acid uptake • platelet-derived growth factor • transforming growth factor-ß
This article has been cited by other articles:
 |
|
 |
|
  A. Zeidan, B. Paylor, K. J. Steinhoff, S. Javadov, V. Rajapurohitam, S. Chakrabarti, and M. Karmazyn Actin Cytoskeleton Dynamics Promotes Leptin-Induced Vascular Smooth Muscle Hypertrophy via RhoA/ROCK- and Phosphatidylinositol 3-Kinase/Protein Kinase B-Dependent Pathways J. Pharmacol. Exp. Ther., September 1, 2007; 322(3): 1110 - 1116. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-A Seong, H. Jung, K.-T. Kim, and H. Ha 3-Phosphoinositide-dependent PDK1 Negatively Regulates Transforming Growth Factor-beta-induced Signaling in a Kinase-dependent Manner through Physical Interaction with Smad Proteins J. Biol. Chem., April 20, 2007; 282(16): 12272 - 12289. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Guilluy, M. Rolli-Derkinderen, P.-L. Tharaux, G. Melino, P. Pacaud, and G. Loirand Transglutaminase-dependent RhoA Activation and Depletion by Serotonin in Vascular Smooth Muscle Cells J. Biol. Chem., February 2, 2007; 282(5): 2918 - 2928. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-A. Seong, H. Jung, H.-S. Choi, K.-T. Kim, and H. Ha Regulation of Transforming Growth Factor-beta Signaling and PDK1 Kinase Activity by Physical Interaction between PDK1 and Serine-Threonine Kinase Receptor-associated Protein J. Biol. Chem., December 30, 2005; 280(52): 42897 - 42908. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Wilkes, H. Mitchell, S. G. Penheiter, J. J. Dore, K. Suzuki, M. Edens, D. K. Sharma, R. E. Pagano, and E. B. Leof Transforming Growth Factor-{beta} Activation of Phosphatidylinositol 3-Kinase Is Independent of Smad2 and Smad3 and Regulates Fibroblast Responses via p21-Activated Kinase-2 Cancer Res., November 15, 2005; 65(22): 10431 - 10440. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Y. Yi, I. Shin, and C. L. Arteaga Type I Transforming Growth Factor {beta} Receptor Binds to and Activates Phosphatidylinositol 3-Kinase J. Biol. Chem., March 18, 2005; 280(11): 10870 - 10876. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.S. Prime, M. Pring, M. Davies, and I.C. Paterson TGF-{beta} SIGNAL TRANSDUCTION IN ORO-FACIAL HEALTH AND NON-MALIGNANT DISEASE (PART I) Crit. Rev. Oral. Biol. Med., November 1, 2004; 15(6): 324 - 336. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Mabrouk, Q. N. Diep, K. Benkirane, R. M. Touyz, and E. L. Schiffrin SAM68: a downstream target of angiotensin II signaling in vascular smooth muscle cells in genetic hypertension Am J Physiol Heart Circ Physiol, May 1, 2004; 286(5): H1954 - H1962. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. E. Runyan, H. W. Schnaper, and A.-C. Poncelet The Phosphatidylinositol 3-Kinase/Akt Pathway Enhances Smad3-stimulated Mesangial Cell Collagen I Expression in Response to Transforming Growth Factor-{beta}1 J. Biol. Chem., January 23, 2004; 279(4): 2632 - 2639. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Dumont, A. V. Bakin, and C. L. Arteaga Autocrine Transforming Growth Factor-beta Signaling Mediates Smad-independent Motility in Human Cancer Cells J. Biol. Chem., January 24, 2003; 278(5): 3275 - 3285. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. E. Mann, D. L. Yudilevich, and L. Sobrevia Regulation of Amino Acid and Glucose Transporters in Endothelial and Smooth Muscle Cells Physiol Rev, January 1, 2003; 83(1): 183 - 252. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Sata and R. Nagai Phosphatidylinositol 3-Kinase: A Key Regulator of Vascular Tone? Circ. Res., August 23, 2002; 91(4): 273 - 275. [Full Text] [PDF]
|
|
|
|
|
|
C. A. Northcott, M. N. Poy, S. M. Najjar, and S. W. Watts Phosphoinositide 3-Kinase Mediates Enhanced Spontaneous and Agonist-Induced Contraction in Aorta of Deoxycorticosterone Acetate-Salt Hypertensive Rats Circ. Res., August 23, 2002; 91(4): 360 - 369. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Reynolds, S. Eguchi, G. D. Frank, and E. D. Motley Signaling Mechanisms of Heparin-Binding Epidermal Growth Factor-Like Growth Factor in Vascular Smooth Muscle Cells Hypertension, February 1, 2002; 39(2): 525 - 529. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. A. Bhowmick, M. Ghiassi, A. Bakin, M. Aakre, C. A. Lundquist, M. E. Engel, C. L. Arteaga, and H. L. Moses Transforming Growth Factor-{beta}1 Mediates Epithelial to Mesenchymal Transdifferentiation through a RhoA-dependent Mechanism Mol. Biol. Cell, January 1, 2001; 12(1): 27 - 36. [Abstract] [Full Text]
|
|
|
|
 |
|
 F. Jung, J. Haendeler, C. Goebel, A. M. Zeiher, and S. Dimmeler Growth factor-induced phosphoinositide 3-OH kinase/Akt phosphorylation in smooth muscle cells: induction of cell proliferation and inhibition of cell death Cardiovasc Res, October 1, 2000; 48(1): 148 - 157. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. V. Bakin, A. K. Tomlinson, N. A. Bhowmick, H. L. Moses, and C. L. Arteaga Phosphatidylinositol 3-Kinase Function Is Required for Transforming Growth Factor beta -mediated Epithelial to Mesenchymal Transition and Cell Migration J. Biol. Chem., November 17, 2000; 275(47): 36803 - 36810. [Abstract] [Full Text] [PDF]
|
|