1: FASEB J. 2004 Apr;18(6):768-70. Epub 2004 Feb 20. 

Platelet-derived growth factor stimulates LAT1 gene expression in vascular
smooth muscle: role in cell growth.

Liu XM, Reyna SV, Ensenat D, Peyton KJ, Wang H, Schafer AI, Durante W.

Michael E. DeBakey VA Medical Center and Department of Medicine, Baylor College
of Medicine, Houston, Texas, USA.

Platelet-derived growth factor (PDGF) contributes to vascular disease by
stimulating the growth of vascular smooth muscle cells (SMCs). Since amino acids
are required for cell growth, the present study examined the effect of PDGF on
system L amino acid transport, which is the predominant cellular pathway for the
uptake of essential amino acids. System L amino acid transport was monitored by
measuring the uptake of L-leucine. Treatment of SMCs with PDGF stimulated
L-leucine transport in a concentration- and time-dependent manner, and this was
associated with a selective increase in LAT1 mRNA and protein. PDGF failed to
induce the expression of the other system L transport proteins, LAT2 and the
heavy chain of the 4F2 cell surface antigen. The induction of LAT1 by PDGF was
dependent on de novo RNA and protein synthesis and on mTOR activity. Serum,
thrombin, and angiotensin II likewise stimulated L-leucine transport by inducing
LAT1 expression. Inhibition of system L amino acid transport by the model
substrate 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid blocked growth
factor-mediated SMC proliferation and induced SMC apoptosis, whereas it had no
effect on quiescent cells. These results demonstrate that growth factors
stimulate system L amino acid transport by inducing LAT1 gene expression and
that system L amino acid transport is essential for SMC proliferation and
survival. The capacity of vascular mitogens to induce LAT1 expression may
represent a basic mechanism by which tho acid transport * apoptosis

PMID: 14977877 [PubMed - indexed for MEDLINE]