Biphasic function of focal adhesion kinase in endothelial tube formation induced by fibril-forming collagens.
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.
Nakamura
Junko
J
Department of Aging Medicine and Geriatrics, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan.
Shigematsu
Satoshi
S
Yamauchi
Keishi
K
Takeda
Teiji
T
Yamazaki
Masanori
M
Kakizawa
Tomoko
T
Hashizume
Kiyoshi
K
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
D024042:Collagen Type I; D024043:Collagen Type II; D005782:Gels; D051417:Focal Adhesion Kinase 1