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Cerebral cavernous malformation gene CCM3 is critical for vascular development by regulating VEGFR2 signaling *
| Content Provider | PubMed Central |
|---|---|
| Author | He, Yun Zhang, Haifeng Yu, Luyang Gunel, Murat Boggon, Titus J. Chen, Hong Min, Wang |
| Abstract | Cerebral cavernous malformations (CCMs) are human vascular malformations caused by mutations in three genes of unknown function: CCM1, CCM2, and CCM3. CCM3, also known as PDCD10 (programmed cell death 10), was initially identified by its mRNA induction by apoptotic stimuli in vitro. However, the in vivo function of CCM3 has not been determined. Here, we describe mice with a deletion of the CCM3 gene either ubiquitously or specifically in certain cell types, including the vascular endothelium, smooth muscle cells, and neurons. Mice with global or endothelial cell-specific deletion of CCM3 die at embryonic stage, exhibiting defects in embryonic angiogenesis. CCM3 deletion reduces VEGFR2 signaling in embryos and derived endothelial cells. CCM3 is recruited to and stabilizes VEGFR2 in response to stimulation by VEGF, and the C-terminal domain of CCM3 is required for the stabilization of VEGFR2. Indeed, the CCM3 mutants found in human patients with a deletion of the C-terminal domain were labile, and unable to stabilize and activate VEGFR2. These results demonstrate that CCM3 regulates vascular development by modulating VEGFR2 signaling. |
| Related Links | http://dx.doi.org/10.1126/scisignal.2000722 |
| Starting Page | 26 |
| File Format | |
| ISSN | 19379145 |
| e-ISSN | 19379145 |
| Journal | Science signaling |
| Issue Number | 116 |
| Volume Number | 3 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Signaling Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
