InsP3R-Ca2+ signaling takes center stage in the hormonal regulation of hepatic gluconeogenesis
During fasting,dephosphorylation-dependent activation of the CREB coactivator CRTC2 by glucagon is crucial for activation of the hepatic gluconeogenic program,but the molecular mechanism by which hormones regulate CRTC2 activation remains unclear.A recent report in Nature showed that PKA-dependent phosphorylation of the inositol-1,4,5-trisphosphate receptor (InsP3R) induces Ca2+ mobilization,leading to increase in the phosphatase activity of calcineurin and the subsequent dephosphorylation of CRTC2,thereby resulting in the induction of gluconeogenic gene expression.It also showed that insulin-dependent phosphorylation of InsP3R by Akt inhibits Ca2+ mobilization and CRTC2 dephosphorylation,resulting in the suppression of gluconeogenesis.
molecular mechanism、gene expression
22
Q2-06
2012-12-28(万方平台首次上网日期,不代表论文的发表时间)
1530-1532