Abstract
The nonreceptor tyrosine kinase focal adhesion kinase (FAK) is a point of convergence for signals from extracellular matrix, soluble factors, and mechanical stimuli. Targeted disruption of the fak gene in mice leads to death at embryonic day 8.5 (E8.5). FAK −/− embryos have severely impaired blood vessel development. Gene expression and in vitro differentiation studies revealed that endothelial cell differentiation was comparable in FAK −/− and wild-type E8.5 embryos. We examined the role of FAK in blood vessel morphogenesis using an in vitro tubulogenesis assay and three different culture systems: FAK +/+ and FAK −/− embryoid bodies, FAK +/+ and FAK −/− endothelial cells, and human umbilical vein endothelial cells expressing antisense FAK, a dominant-negative fragment of FAK, or wild-type FAK. In all of these systems, endothelial cells deficient in FAK expression or function displayed a severely reduced ability to form tubules in Matrigel. These studies demonstrate clearly that the vascular defects in FAK −/− mice result from the inability of FAK-deficient endothelial cells to organize themselves into vascular networks, rather than from defects in tissue-specific differentiation.
References
39
Referenced
93
10.1038/386671a0
10.1038/376062a0
10.1242/dev.119.4.1079
10.1242/dev.119.4.1093
10.1002/(SICI)1097-0177(199610)207:2<145::AID-AJA3>3.0.CO;2-H
10.1016/S0092-8674(00)81848-6
10.1038/71517
10.1073/pnas.96.26.14888
10.1073/pnas.98.2.620
10.1126/science.284.5415.808
10.1016/S0079-6107(98)00052-2
10.1083/jcb.147.3.611
- Furuta Y, Ilic D, Kanazawa S, Takeda N, Yamamoto T, Aizawa S. Mesodermal defect in late phase of gastrulation by a targeted mutation of focal adhesion kinase, FAK. Oncogene. 1995; 11: 1989–1995. / Oncogene (1995)
10.1038/377539a0
10.1182/blood.V90.8.3073
10.1083/jcb.143.2.547
- Tsukada Y, Tomooka Y, Takai S, Ueda Y, Nishikawa S, Yagi T, Tokunaga T, Takeda N, Suda Y, Abe S, Matsuo I, Ikawa Y, Aizawa S. Enhanced proliferative potential in culture of cells from p53-deficient mice. Oncogene. 1993; 8: 3313–3322. / Oncogene (1993)
10.1073/pnas.72.4.1441
10.1242/dev.114.2.303
10.1006/excr.1996.0038
10.1006/abio.1993.1458
10.1016/S0002-9440(10)65366-7
10.1093/emboj/17.20.5933
10.1074/jbc.273.52.35185
10.1128/JVI.71.3.1842-1849.1997
10.1016/S0002-9440(10)61677-X
10.1091/mbc.12.8.2290
10.1242/dev.125.8.1457
10.1083/jcb.149.3.741
10.1097/00062752-199901000-00008
10.1002/1097-4652(2001)9999:9999<00::AID-JCP1051>3.0.CO;2-F
10.1093/oxfordjournals.jbchem.a123903
10.1242/dev.121.1.37
10.1242/dev.120.9.2539
10.1242/dev.126.3.535
10.1007/BF01680633
10.1006/bbrc.1995.1503
- CenterWatch Clinical Trials Listing Service. Available at: http://www.centerwatch.com.
- National Cancer Institute clinical trials. Available at: http://www.cancer.gov/clinicaltrials.
Dates
Type | When |
---|---|
Created | 22 years, 6 months ago (Feb. 20, 2003, 6:38 p.m.) |
Deposited | 1 year, 3 months ago (May 12, 2024, 2:36 p.m.) |
Indexed | 2 months, 3 weeks ago (June 3, 2025, 11:14 a.m.) |
Issued | 22 years, 6 months ago (Feb. 21, 2003) |
Published | 22 years, 6 months ago (Feb. 21, 2003) |
Published Print | 22 years, 6 months ago (Feb. 21, 2003) |
@article{Ilic_2003, title={Focal Adhesion Kinase Is Required for Blood Vessel Morphogenesis}, volume={92}, ISSN={1524-4571}, url={http://dx.doi.org/10.1161/01.res.0000055016.36679.23}, DOI={10.1161/01.res.0000055016.36679.23}, number={3}, journal={Circulation Research}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Ilic, Dusko and Kovacic, Branka and McDonagh, Susan and Jin, Fang and Baumbusch, Clark and Gardner, David G. and Damsky, Caroline H.}, year={2003}, month=feb, pages={300–307} }