High impact information on Rapgef4

• cAMP-GEFII is a direct target of cAMP in regulated exocytosis [1].
• These data suggest that the interactions of the KATP channel, cAMP-GEFII, Piccolo, and L-type VDCC are regulated by intracellular signals such as cAMP and Ca2+ and that the ATP, cAMP, and Ca2+ signals are integrated at a specialized region of pancreatic beta-cells [2].
• We have previously shown that cAMP-binding protein cAMP-guanidine nucleotide exchange factor II (GEFII) (or Epac2) interacting with Rim2 is involved in cAMP-dependent, protein kinase A-independent exocytosis in pancreatic beta-cells [3].
• Treatment of pancreatic islets with antisense oligodeoxynucleotides (ODNs) against cAMP-GEFII alone or with the PKA inhibitor H-89 alone inhibited incretin-potentiated insulin secretion approximately 50%, while a combination of antisense ODNs and H-89 inhibited the secretion approximately 80-90% [4].
• Moreover, treatment of B-cells with antisense oligodeoxynucleotides against cAMP-GEFII resulted in partial (50%) suppression of PKA-independent exocytosis [5].

Biological context of Rapgef4

• Exchange protein directly activated by cyclic AMP 2 (Epac2, or cAMP-binding guanine nucleotide exchange factor-2) was found to be expressed in gut and pancreatic proglucagon-producing cell lines, whereas the Epac-pathway-specific cAMP analog, 8-pMeOPT-2'O-Me-cAMP, effectively stimulated ERK1/2 phosphorylation as well as proglucagon mRNA expression [6].
• Here we report the three-dimensional structure of full-length Epac2, a 110-kDa protein that contains an amino-terminal regulatory region with two cyclic-nucleotide-binding domains and a carboxy-terminal catalytic region [7].
• Analyses by primer extension, reverse transcriptase-polymerase chain reaction, and in situ hybridization revealed the presence of three transcription start sites of liver-specific Epac2: two major sites located in exon 10 and a minor site in intron 9 [8].

Associations of Rapgef4 with chemical compounds

• Differential modulation of Cav1.2 and Cav1.3-mediated glucose-stimulated insulin secretion by cAMP in INS-1 cells: distinct roles for exchange protein directly activated by cAMP 2 (Epac2) and protein kinase A [9].

Other interactions of Rapgef4

• Furthermore, cAMP modulation of secretion mediated by Cav1.2 seems to involve both Epac2 and PKA independently [9].

References