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Modulation of amino acid uptake by TGF‐β in lung myofibroblasts
Author(s) -
Subramanian Mangalalaxmy,
Kuang PingPing,
Wei Lin,
Rishikof David C.,
Liu Hanqiao,
Goldstein Ronald H.
Publication year - 2006
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.20849
Subject(s) - protein kinase b , ly294002 , kinase , amino acid transporter , phosphorylation , phosphatidylinositol , pi3k/akt/mtor pathway , transforming growth factor , chemistry , amino acid , microbiology and biotechnology , signal transduction , biology , biochemistry , transporter , gene
Abstract Hormones such as insulin, growth factors, and cell stress stimulate system A amino acid transporter. Transforming growth factor‐β (TGF‐β) stimulates amino acid uptake thereby inducing cell proliferation, cellular hypertrophy, and matrix synthesis. Insulin appears to activate amino acid in smooth muscle cells via a phosphatidylinositol 3‐kinase (PI3‐kinase)‐dependent pathway. We examine the effect and interaction of TGF‐β, insulin, and PI3‐kinase activity on amino acid uptake in human lung myofibroblasts. TGF‐β treatment induced large increases in system A activity and a small delayed increase in the phosphorylation of protein kinase B, also termed phospho‐Akt. In contrast, insulin induced small increases in system A activity and large increases in phospho‐Akt levels. LY294002, a PI3‐kinase inhibitor, blocked the TGF‐β‐induced amino acid uptake only partially, but completely blocked TGF‐β‐induced Akt phosphorylation. Moreover, the level of phospho‐Smad3 was found to be high even when LY294002 blocked TGF‐β‐induced phospho‐Akt levels. Inhibition of PI3‐kinase activity resulted in increase in K m , consistent with a major change in transporter activity without change in transporter number. The PI3‐kinase inhibitor also did not change the amino acid transporter 2 (ATA2) mRNA levels. Taken together, these results suggest that TGF‐β induced Smad‐3 and amino acid uptake through a PI3‐kinase independent pathway. © 2006 Wiley‐Liss, Inc.