Differential influence of cAMP on the expression of the three subtypes (ATA1, ATA2, and ATA3) of the amino acid transport system A

Treatment of HepG2 cells with forskolin led to 60-100% stimulation of syste m A activity, measured as the Na+-dependent uptake of alpha-(methylamino)is obutyric acid. The stimulation was reproducible with cholera toxin and dibu tyryl cAMP, and inhibitable by H7, a non-specific protein kinase inhibitor. The stimulatory effect was eliminated by cycloheximide and actinomycin D. The forskolin effect was associated with an increase in the maximal velocit y of the transport system, with no change in substrate affinity. These cell s express three different subtypes of system A (ATA1, ATA2, and ATA3). Trea tment with forskolin increased the steady-state levels of ATA1 and ATA2 mRN As, but decreased that of ATA3 mRNA. (C) 2001 Federation of European Bioche mical Societies. Published by Elsevier Science B.V. All rights reserved.