, Volume 53, Issue 8, pp 2113-2125
Date: 20 Dec 2007

In Human Entrocytes, GLN Transport and ASCT2 Surface Expression Induced by Short-Term EGF are MAPK, PI3K, and Rho-Dependent

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Abstract

Glutamine, a key nutrient for the enterocyte, is transported among other proteins by ASCT2. Epidermal growth factor (EGF) augments intestinal adaptation. We hypothesized that short-term treatment of human enterocytes with EGF enhances glutamine transport by increasing membranal ASCT2. To elucidate EGF-induced mechanisms, monolayers of C2BBe1 w/wo siRho transfection were treated w/wo EGF and w/wo tyrphostin AG1478 (AG1478), wortmanin, or PD98059. Total and system-specific 3H-glutamine transports were determined w/wo 5 mmol/l amino acid inhibitors. Total and membranal ASCT2 proteins were measured by Westerns. EGF doubled glutamine transport by increasing B0/ASCT2 and B0,+ activities. Despite the doubling of membranal ASCT2 protein with EGF treatment, total ASCT2 did not change. The increases in B0/ASCT2 activity and ASCT2 protein were eliminated by AG1478, PD98059, wortmanin, and siRho, while transport by B0,+ was inhibited only by PD98059 and siRho. Thus, differential pathways are involved in EGF-induced increase in B0/ASCT2 glutamine transport and membranal ASCT2 compared to those involved in B0,+ activity.

Supported by NIH 5 RO1 DK47989-10.