Regulation of Na(+)-coupled glucose transport in LLC-PK1 cells. Message stabilization induced by cyclic AMP elevation is accompanied by binding of a M(r) = 48,000 protein to a uridine-rich domain in the 3'-untranslated region.

In an exploration of the molecular basis of cyclic AMP-induced stabilization of Na+/glucose cotransporter mRNA (SGLT1 isoform) accompanying cell differentiation in the pig kidney cell line LLC-PK1, we have identified a 48-kDa cytoplasmic protein factor, designated SG-URBP, which specifically binds a 120-nucleotide sequence within the 3'-untranslated region of the SGLT1 message. A 46-nucleotide uridine-rich element within this region appears necessary for specific binding, and the presence of the 3'-untranslated region is necessary for message stabilization by cyclic AMP. The binding activity of SG-URBP is up-regulated after cyclic AMP elevation and protein kinase A activation, whereas protein dephosphorylation either in vivo or in vitro is associated with loss of binding activity. The increase in SG-URBP binding activity correlates with an increase in the half-life of the SGLT1 message, suggesting a cause and effect relationship.