Disease relevance of Rapgef1

• Animal studies showed that C3G reduced the size of A549 tumor xenograft growth and significantly inhibited metastasis in nude mice [1].
• At the highest doses of C3G and Mirtoselect adenoma numbers were decreased by 45% (p < 0.001) or 30% (p < 0.05), respectively, compared to controls [2].
• The efficacy of C3G and Mirtoselect in the Apc(Min) mouse renders the further development of anthocyanins as potential human colorectal cancer chemopreventive agents worthwhile [2].

High impact information on Rapgef1

• C3G is a guanine nucleotide exchange factor for members of the Ras family of GTPases [3].
• The guanine nucleotide exchange factor C3G is necessary for the formation of focal adhesions and vascular maturation [3].
• C3G-deficient fibroblasts responded to PDGF-BB abnormally, exhibited cell adhesion defects and lacked paxillin and integrin-beta1-positive cell adhesions [3].
• Cyanidin-3-glucoside (C3G), a compound found in blackberry and other food products, was shown to possess chemopreventive and chemotherapeutic activity in the present study [1].
• In addition, C3G inhibited proliferation of a human lung carcinoma cell line, A549 [1].

Biological context of Rapgef1

• We report that Reelin stimulates tyrosine phosphorylation of C3G and activates Rap1 [4].
• These results indicate that two C3G mRNAs and proteins result from alternative RNA splicing [5].
• Sequence comparison revealed 88% nucleotide sequence identity between mouse and human C3G cDNA [5].
• Comparison of mouse C3G cDNA with the human genome database suggested that this 114-bp sequence comprised an entire exon, and it is confirmed by PCR analysis using mouse genomic DNA and cDNA template [5].
• Two types of C3G cDNA were isolated from mouse 3T3-L1 adipocyte cDNA library [5].

Anatomical context of Rapgef1

• Adhesion-induced tyrosine phosphorylation of C3G is dependent on an intact cytoskeleton and peaks at 5-10 min after attachment [6].
• Mouse Schwann cells (MSCs) express R-Ras and TC21/R-Ras2 and their specific guanine exchange factors, C3G and AND-34 [7].
• Total anthocyanin levels in mice on C3G or Mirtoselect were 43 ng and 8.1 mug/g tissue, respectively, in the intestinal mucosa, and 7.2 and 12.3 mug/ml in the urine [2].
• In the present study, we examined the effect of d-glucose (main substrate of SGLT1), phloridzin (inhibitor of SGLT1), and quercetin-3-glucose (Q3G, a flavonol) on the absorption of cyanidin-3-glucoside (C3G; approximately 5 micromol/L) by mouse jejunum mounted in Ussing chambers [8].
• Disruption of flotillin-1-based domains prevents the activation of C3G, movement of GLUT4 to the sarcolemma, and glucose uptake in response to insulin [9].

Associations of Rapgef1 with chemical compounds

• In cultured JB6 cells, C3G was able to scavenge ultraviolet B-induced *OH and O2-* radicals [1].
• We found that the presence of either D-glucose (10, 20, and 40 mmol/L) or phloridzin (50, 100, and 200 micromol/L) resulted in a small but insignificant inhibition of C3G disappearance from the mucosal solution (decrease of disappearance with glucose, 33%; with phloridzin, 18%; NS) [8].
• However, when the flavonol Q3G (50 micromol/L) was added to the mucosal solution together with the C3G, the disappearance of C3G was significantly decreased (74%; p < 0.001), and Q3G disappeared instead [8].

Regulatory relationships of Rapgef1

• C3G is activated in response to reelin in cortical neurons, which, in turn, leads to activation of the small GTPase Rap1 [10].

Other interactions of Rapgef1

• These data indicate that GPCRs coupled to pertussis-toxin-sensitive G-proteins activate Rap through a Galpha subunit, C3G, and Src-dependent pathway [11].

Analytical, diagnostic and therapeutic context of Rapgef1

• By RT-PCR analysis, it was found that these two types of C3G mRNA existed in all the mouse tissues [5].

References