title: Biphasic function of focal adhesion kinase in endothelial tube formation induced by fibril-forming collagens.
abstract: Migration and tube formation of endothelial cells are important in angiogenesis and require a coordinated response to the extra-cellular matrix (ECM) and growth factor. Since focal adhesion kinase (FAK) integrates signals from both ECM and growth factor, we investigated its role in angiogenesis. Type I and II collagens are fibril-forming collagens and stimulate human umbilical vein endothelial cells (HUVECs) to form tube structure. Although knockdown of FAK restrained cell motility and resulted in inhibition of tube formation, FAK degradation and tube formation occurred simultaneously after incubation with fibril-forming collagens. The compensation for the FAK degradation by a calpain inhibitor or transient over-expression of FAK resulted in disturbance of tube formation. These phenomena are specific to fibril-forming collagens and mediated via alpha2beta1 integrin. In conclusion, our data indicate that FAK is functioning in cell migration, but fibril-forming collagen-induced FAK degradation is necessary for endothelial tube formation.
authors.affiliation: Department of Aging Medicine and Geriatrics, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Nakamura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Shigematsu
authors.forename: Keishi
authors.initials: K
authors.lastname: Yamauchi
authors.forename: Teiji
authors.initials: T
authors.lastname: Takeda
authors.forename: Masanori
authors.initials: M
authors.lastname: Yamazaki
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kakizawa
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hashizume
mesh_terms: D000818:Animals; D002465:Cell Movement; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism*; D024043:Collagen Type II / Q000378:metabolism*; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000166:cytology / Q000254:growth & development*; D051417:Focal Adhesion Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005782:Gels; D006801:Humans; D018919:Neovascularization, Physiologic; D051381:Rats
chemical_list: D024042:Collagen Type I; D024043:Collagen Type II; D005782:Gels; D051417:Focal Adhesion Kinase 1