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 system A activity, measured as the Na+-dependent uptake of alpha-(methylamino)isobutyric acid. The stimulation was reproducible with cholera toxin and dibutyryl 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 velocity of the transport system, with no change in substrate affinity. These cells express three different subtypes of system A (ATA1, ATA2, and ATA3). Treatment with forskolin increased the steady-state levels of ATA1 and ATA2 mRNAs, but decreased that of ATA3 mRNA.
Hatanaka
T
T
Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, GA 30912, USA.
Huang
W
W
Martindale
R G
RG
Ganapathy
V
V
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D026905:Amino Acid Transport Systems; D000596:Amino Acids / Q000378:metabolism*; D000621:Aminoisobutyric Acids / Q000494:pharmacology; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D002772:Cholera Toxin / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D011061:Poly A / Q000378:metabolism; D011485:Protein Binding; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D013379:Substrate Specificity; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D026905:Amino Acid Transport Systems; D000596:Amino Acids; D000621:Aminoisobutyric Acids; D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D003609:Dactinomycin; D005576:Colforsin; D011061:Poly A; C017911:2-(methylamino)isobutyric acid; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D002772:Cholera Toxin; D003513:Cycloheximide; D012964:Sodium; D000242:Cyclic AMP