Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Sci. Signal., 6 April 2010
Vol. 3, Issue 116, p. ra26
[DOI: 10.1126/scisignal.2000722]

RESEARCH ARTICLES

Editor's Summary

Stability for Blood Vessel Formation
Cerebral cavernous malformations (CCMs) are commonly occurring, thin-walled dilations of the vasculature of the central nervous system. Although these defects can arise spontaneously, most cases are caused by mutations in the genes encoding the CCM proteins. How CCM3 contributes to these vascular defects is unknown. He et al. found that mice that were globally deficient for CCM3 or specifically deficient in endothelial cells died because of defects in angiogenesis during development. CCM3 deficiency reduced the activity of vascular endothelial growth factor receptor 2 (VEGFR2), which is required for hematopoiesis and vasculogenesis. VEGF stimulation promoted the interaction of CCM3 with VEGFR2, an association that prevented VEGF-induced internalization and degradation of VEGFR2. Three CCM3 mutant proteins associated with CCMs in humans were unstable and enhanced the degradation of VEGFR2. Thus, CCM3 is required to promote VEGFR2 signaling during vascular development.

Citation: Y. He, H. Zhang, L. Yu, M. Gunel, T. J. Boggon, H. Chen, W. Min, Stabilization of VEGFR2 Signaling by Cerebral Cavernous Malformation 3 Is Critical for Vascular Development. Sci. Signal. 3, ra26 (2010).

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Ccm3, a gene associated with cerebral cavernous malformations, is required for neuronal migration.
A. Louvi, S. Nishimura, and M. Gunel (2014)
Development 141, 1404-1415
   Abstract »    Full Text »    PDF »
AIP1 Mediates Vascular Endothelial Cell Growth Factor Receptor-3-Dependent Angiogenic and Lymphangiogenic Responses.
H. J. Zhou, X. Chen, Q. Huang, R. Liu, H. Zhang, Y. Wang, Y. Jin, X. Liang, L. Lu, Z. Xu, et al. (2014)
Arterioscler Thromb Vasc Biol 34, 603-615
   Abstract »    Full Text »    PDF »
Cerebral cavernous malformation proteins at a glance.
K. M. Draheim, O. S. Fisher, T. J. Boggon, and D. A. Calderwood (2014)
J. Cell Sci. 127, 701-707
   Abstract »    Full Text »    PDF »
Endothelial Cell-to-Cell Junctions: Adhesion and Signaling in Physiology and Pathology.
M. G. Lampugnani (2012)
Cold Spring Harb Perspect Med 2, a006528
   Abstract »    Full Text »    PDF »
SCF{beta}-TRCP suppresses angiogenesis and thyroid cancer cell migration by promoting ubiquitination and destruction of VEGF receptor 2.
S. Shaik, C. Nucera, H. Inuzuka, D. Gao, M. Garnaas, G. Frechette, L. Harris, L. Wan, H. Fukushima, A. Husain, et al. (2012)
J. Exp. Med. 209, 1289-1307
   Abstract »    Full Text »    PDF »
Adaptor Protein Cerebral Cavernous Malformation 3 (CCM3) Mediates Phosphorylation of the Cytoskeletal Proteins Ezrin/Radixin/Moesin by Mammalian Ste20-4 to Protect Cells from Oxidative Stress.
M. Fidalgo, A. Guerrero, M. Fraile, C. Iglesias, C. M. Pombo, and J. Zalvide (2012)
J. Biol. Chem. 287, 11556-11565
   Abstract »    Full Text »    PDF »
Developmental timing of CCM2 loss influences cerebral cavernous malformations in mice.
G. Boulday, N. Rudini, L. Maddaluno, A. Blecon, M. Arnould, A. Gaudric, F. Chapon, R. H. Adams, E. Dejana, and E. Tournier-Lasserve (2011)
J. Exp. Med. 208, 1835-1847
   Abstract »    Full Text »    PDF »
Conditional deletion of Ccm2 causes hemorrhage in the adult brain: a mouse model of human cerebral cavernous malformations.
K. Cunningham, Y. Uchida, E. O'Donnell, E. Claudio, W. Li, K. Soneji, H. Wang, Y.-s. Mukouyama, and U. Siebenlist (2011)
Hum. Mol. Genet. 20, 3198-3206
   Abstract »    Full Text »    PDF »
Molecular Recognition of Leucine-Aspartate Repeat (LD) Motifs by the Focal Adhesion Targeting Homology Domain of Cerebral Cavernous Malformation 3 (CCM3).
X. Li, W. Ji, R. Zhang, E. Folta-Stogniew, W. Min, and T. J. Boggon (2011)
J. Biol. Chem. 286, 26138-26147
   Abstract »    Full Text »    PDF »
CCM3/PDCD10 Heterodimerizes with Germinal Center Kinase III (GCKIII) Proteins Using a Mechanism Analogous to CCM3 Homodimerization.
D. F. Ceccarelli, R. C. Laister, V. K. Mulligan, M. J. Kean, M. Goudreault, I. C. Scott, W. B. Derry, A. Chakrabartty, A.-C. Gingras, and F. Sicheri (2011)
J. Biol. Chem. 286, 25056-25064
   Abstract »    Full Text »    PDF »
Loss of cerebral cavernous malformation 3 (Ccm3) in neuroglia leads to CCM and vascular pathology.
A. Louvi, L. Chen, A. M. Two, H. Zhang, W. Min, and M. Gunel (2011)
PNAS 108, 3737-3742
   Abstract »    Full Text »    PDF »
PDCD10/CCM3 Acts Downstream of {gamma}-Protocadherins to Regulate Neuronal Survival.
C. Lin, S. Meng, T. Zhu, and X. Wang (2010)
J. Biol. Chem. 285, 41675-41685
   Abstract »    Full Text »    PDF »
Evaluating Strategies for the Treatment of Cerebral Cavernous Malformations.
D. Y. Li and K. J. Whitehead (2010)
Stroke 41, S92-S94
   Abstract »    Full Text »    PDF »
Crystal Structure of CCM3, a Cerebral Cavernous Malformation Protein Critical for Vascular Integrity.
X. Li, R. Zhang, H. Zhang, Y. He, W. Ji, W. Min, and T. J. Boggon (2010)
J. Biol. Chem. 285, 24099-24107
   Abstract »    Full Text »    PDF »
Gyrate: CCM3 Dances with a Different Angiogenic Partner.
L. A. Dyer, A. L. Portbury, and C. Patterson (2010)
Science Signaling 3, pe17
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882