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.
机构:
Kobe Univ, Grad Sch Med, Dept Biochem & Mol Biol, Div Mol Biol,Chuo Ku, Kobe, Hyogo 6500017, Japan
Suez Canal Univ, Fac Pharm, Dept Biochem, Ismailia 41522, EgyptKobe Univ, Grad Sch Med, Dept Biochem & Mol Biol, Div Mol Biol,Chuo Ku, Kobe, Hyogo 6500017, Japan
Bilasy, Shymaa E.
Satoh, Takaya
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Kobe Univ, Grad Sch Med, Dept Biochem & Mol Biol, Div Mol Biol,Chuo Ku, Kobe, Hyogo 6500017, JapanKobe Univ, Grad Sch Med, Dept Biochem & Mol Biol, Div Mol Biol,Chuo Ku, Kobe, Hyogo 6500017, Japan
Satoh, Takaya
Terashima, Toshio
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机构:
Kobe Univ, Grad Sch Med, Dept Physiol & Cell Biol, Div Dev Neurobiol,Chuo Ku, Kobe, Hyogo 6500017, JapanKobe Univ, Grad Sch Med, Dept Biochem & Mol Biol, Div Mol Biol,Chuo Ku, Kobe, Hyogo 6500017, Japan
Terashima, Toshio
Kataoka, Tohru
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机构:
Kobe Univ, Grad Sch Med, Dept Biochem & Mol Biol, Div Mol Biol,Chuo Ku, Kobe, Hyogo 6500017, JapanKobe Univ, Grad Sch Med, Dept Biochem & Mol Biol, Div Mol Biol,Chuo Ku, Kobe, Hyogo 6500017, Japan
机构:
Cold Spring Harbor Lab, Watson Sch Biol Sci, Cold Spring Harbor, NY 11724 USACold Spring Harbor Lab, Watson Sch Biol Sci, Cold Spring Harbor, NY 11724 USA
Boettner, Benjamin
Van Aelst, Linda
论文数: 0引用数: 0
h-index: 0
机构:
Cold Spring Harbor Lab, Watson Sch Biol Sci, Cold Spring Harbor, NY 11724 USACold Spring Harbor Lab, Watson Sch Biol Sci, Cold Spring Harbor, NY 11724 USA
机构:
Kobe Univ, Grad Sch Med, Dept Biochem & Mol Biol, Div Mol Biol,Chuo Ku, Kobe, Hyogo 6500017, Japan
Suez Canal Univ, Fac Pharm, Dept Biochem, Ismailia 41522, EgyptKobe Univ, Grad Sch Med, Dept Biochem & Mol Biol, Div Mol Biol,Chuo Ku, Kobe, Hyogo 6500017, Japan
Bilasy, Shymaa E.
Satoh, Takaya
论文数: 0引用数: 0
h-index: 0
机构:
Kobe Univ, Grad Sch Med, Dept Biochem & Mol Biol, Div Mol Biol,Chuo Ku, Kobe, Hyogo 6500017, JapanKobe Univ, Grad Sch Med, Dept Biochem & Mol Biol, Div Mol Biol,Chuo Ku, Kobe, Hyogo 6500017, Japan
Satoh, Takaya
Terashima, Toshio
论文数: 0引用数: 0
h-index: 0
机构:
Kobe Univ, Grad Sch Med, Dept Physiol & Cell Biol, Div Dev Neurobiol,Chuo Ku, Kobe, Hyogo 6500017, JapanKobe Univ, Grad Sch Med, Dept Biochem & Mol Biol, Div Mol Biol,Chuo Ku, Kobe, Hyogo 6500017, Japan
Terashima, Toshio
Kataoka, Tohru
论文数: 0引用数: 0
h-index: 0
机构:
Kobe Univ, Grad Sch Med, Dept Biochem & Mol Biol, Div Mol Biol,Chuo Ku, Kobe, Hyogo 6500017, JapanKobe Univ, Grad Sch Med, Dept Biochem & Mol Biol, Div Mol Biol,Chuo Ku, Kobe, Hyogo 6500017, Japan
机构:
Cold Spring Harbor Lab, Watson Sch Biol Sci, Cold Spring Harbor, NY 11724 USACold Spring Harbor Lab, Watson Sch Biol Sci, Cold Spring Harbor, NY 11724 USA
Boettner, Benjamin
Van Aelst, Linda
论文数: 0引用数: 0
h-index: 0
机构:
Cold Spring Harbor Lab, Watson Sch Biol Sci, Cold Spring Harbor, NY 11724 USACold Spring Harbor Lab, Watson Sch Biol Sci, Cold Spring Harbor, NY 11724 USA