TGF-beta transcriptionally activates the gene encoding the high-affinity adenosine transporter CNT2 in rat liver parenchymal cells.
The nucleoside transporter CNT2 is the highest-affinity adenosine transporter identified so far. Recent evidence suggests that CNT2 has functions other than salvage (i.e. modulation of purinergic responses). Here we identified TGF-beta1 as a potent inducer of CNT2 protein expression in liver parenchymal cells. By contrast, CNT1, which is a target of multifunctional cytokines involved in liver cell proliferation, does not respond to TGF-beta1 treatment. Cloning of a murine CNT2 gene sequence with promoter-like activity enabled us to demonstrate that this cytokine exerts this effect by transcriptionally activating the CNT2-encoding gene in a JNK-dependent manner. The evidence that CNT2 is not a target of multifunctional cytokines involved in hepatocyte proliferation, but instead, of a cytokine that plays major roles in differentiation and apoptosis, further supports the view that the main physiological role of this transporter protein is not nucleoside salvage.
Valdés
R
R
Department of Biochemistry and Molecular Biology, School of Biology, University of Barcelona, Diagonal 645, 08028, Barcelona, Spain.
Fernández-Veledo
S
S
Aymerich
I
I
Casado
F J
FJ
Pastor-Anglada
M
M
D024506:5' Flanking Region / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D003907:Dexamethasone / Q000494:pharmacology; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects*; D026901:Membrane Transport Proteins / Q000235:genetics*; D051379:Mice; D051381:Rats; D017384:Sequence Deletion / Q000235:genetics; D015533:Transcriptional Activation / Q000187:drug effects*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
D026901:Membrane Transport Proteins; D053773:Transforming Growth Factor beta1; C065171:cif nucleoside transporter; D003907:Dexamethasone