| First Author | Sivaraj KK | Year | 2013 |
| Journal | Dev Cell | Volume | 25 |
| Issue | 4 | Pages | 427-34 |
| PubMed ID | 23664862 | Mgi Jnum | J:316448 |
| Mgi Id | MGI:6837168 | Doi | 10.1016/j.devcel.2013.04.008 |
| Citation | Sivaraj KK, et al. (2013) G13 controls angiogenesis through regulation of VEGFR-2 expression. Dev Cell 25(4):427-34 |
| abstractText | At sites of angiogenesis, the expression of the key angiogenesis regulator vascular endothelial growth factor (VEGF) and its main receptor, VEGF receptor 2 (VEGFR-2), are strongly upregulated. Whereas the processes controlling VEGF expression are well described, the mechanisms underlying VEGFR-2 upregulation have remained unclear. We found that endothelial VEGFR-2 expression is strongly reduced in the absence of the G protein G13, resulting in an impaired responsiveness to VEGF-A, a phenotype that can be rescued by normalization of VEGFR-2 levels. G13-mediated VEGFR-2 expression involved activation of the small GTPase RhoA and transcription factor NF-kappaB, the latter acting via a specific binding site at position -84 of the VEGFR-2 promoter. Mice with endothelial cell-specific loss of G13 showed reduced VEGFR-2 expression at sites of angiogenesis and attenuated VEGF effects, resulting in impaired retinal angiogenesis and tumor vascularization. Taken together, we identified G-protein-mediated signaling via G13 as a critical regulator of VEGFR-2 expression during angiogenesis. |
