| First Author | Emery AC | Year | 2013 |
| Journal | Sci Signal | Volume | 6 |
| Issue | 281 | Pages | ra51 |
| PubMed ID | 23800469 | Mgi Jnum | J:201420 |
| Mgi Id | MGI:5514088 | Doi | 10.1126/scisignal.2003993 |
| Citation | Emery AC, et al. (2013) Rapgef2 connects GPCR-mediated cAMP signals to ERK activation in neuronal and endocrine cells. Sci Signal 6(281):ra51 |
| abstractText | G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor (GPCR)-mediated increases in the second messenger cyclic adenosine monophosphate (cAMP) activate the mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase (ERK), and in neuroendocrine cells, this pathway leads to cAMP-dependent neuritogenesis mediated through Rap1 and B-Raf. We found that the Rap guanine nucleotide exchange factor Rapgef2 was enriched from primary bovine neuroendocrine cells by cAMP-agarose affinity chromatography and that it was specifically eluted by cAMP. With loss-of-function experiments in the rat neuronal cell line Neuroscreen-1 (NS-1) and gain-of-function experiments in human embryonic kidney 293T cells, we demonstrated that Rapgef2 connected GPCR-dependent activation of adenylate cyclase and increased cAMP concentration with the activation of ERK in neurons and endocrine cells. Furthermore, knockdown of Rapgef2 blocked cAMP- and ERK-dependent neuritogenesis. Our data are consistent with a pathway involving the cAMP-mediated activation of Rapgef2, which then stimulates Rap1, leading to increases in B-Raf, MEK, and ERK activity. |
