Integrin-mediated mechanotransduction requires its dynamic interaction with specific extracellular matrix (ECM) ligands

被引:323
作者
Jalali, S
del Pozo, MA
Chen, KD
Miao, H
Li, YS
Schwartz, MA
Shyy, JYJ
Chien, S
机构
[1] Univ Calif San Diego, Whitehead Inst Biomed Res, La Jolla, CA 92093 USA
[2] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA
[3] Scripps Res Inst, Dept Vasc Biol, La Jolla, CA 92037 USA
[4] Univ Calif Riverside, Div Biomed Sci, Riverside, CA 92521 USA
关键词
shear stress; endothelial cell; signal transduction;
D O I
10.1073/pnas.031562998
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The aim of this study is to elucidate the role of integrins in transducing fluid shear stress into intracellular signals in vascular endothelial cells, a fundamental process in vascular biology, We demonstrated that shear stress activates specific integrins in endothelial cells plated on substrates containing the cognate extracellular matrix (ECM) ligands. The shear stress-induced mechanotransduction, as manifested by integrin-Shc association, was abolished when new integrin-ECM ligand interactions were prevented by either blocking the integrin-binding sites of ECM ligands or conjugating the integrins to immobilized antibodies, Our results indicate that the dynamic formation of new connections between integrins and their specific ECM ligands is critical in relaying the signals induced by shear stress to intracellular pathways.
引用
收藏
页码:1042 / 1046
页数:5
相关论文
共 23 条
[1]  
BURRIDGE K, 1988, ANNU REV CELL BIOL, V4, P487, DOI 10.1146/annurev.cb.04.110188.002415
[2]   Mechanotransduction in response to shear stress - Roles of receptor tyrosine kinases, integrins, and Shc [J].
Chen, KD ;
Li, YS ;
Kim, M ;
Li, S ;
Yuan, S ;
Chien, S ;
Shyy, JYJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (26) :18393-18400
[3]   Effects of mechanical forces on signal transduction and gene expression in endothelial cells [J].
Chien, S ;
Li, S ;
Shyy, JYJ .
HYPERTENSION, 1998, 31 (01) :162-169
[4]   FLOW-MEDIATED ENDOTHELIAL MECHANOTRANSDUCTION [J].
DAVIES, PF .
PHYSIOLOGICAL REVIEWS, 1995, 75 (03) :519-560
[5]   QUANTITATIVE STUDIES OF ENDOTHELIAL-CELL ADHESION - DIRECTIONAL REMODELING OF FOCAL ADHESION SITES IN RESPONSE TO FLOW FORCES [J].
DAVIES, PF ;
ROBOTEWSKYJ, A ;
GRIEM, ML .
JOURNAL OF CLINICAL INVESTIGATION, 1994, 93 (05) :2031-2038
[6]   FLOW EFFECTS ON PROSTACYCLIN PRODUCTION BY CULTURED HUMAN-ENDOTHELIAL CELLS [J].
FRANGOS, JA ;
ESKIN, SG ;
MCINTIRE, LV ;
IVES, CL .
SCIENCE, 1985, 227 (4693) :1477-1479
[7]   Phosphatidylinositol 3-kinase γ mediates shear stress-dependent activation of JNK in endothelial cells [J].
Go, YM ;
Park, HY ;
Maland, MC ;
Darley-Usmar, VM ;
Stoyanov, B ;
Wetzker, R ;
Jo, HJ .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 1998, 275 (05) :H1898-H1904
[8]   Functional relevance during lymphocyte migration and cellular localization of activated beta 1 integrins [J].
Gomez, M ;
Luque, A ;
delPozo, MA ;
Hogg, N ;
SanchezMadrid, F ;
Cabanas, C .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1997, 27 (01) :8-16
[9]   Suppression of integrin activation: A novel function of a Ras/Raf-initiated MAP kinase pathway [J].
Hughes, PE ;
Renshaw, MW ;
Pfaff, M ;
Forsyth, J ;
Keivens, VM ;
Schwartz, MA ;
Ginsberg, MH .
CELL, 1997, 88 (04) :521-530
[10]   Modulation of cell migration by integrin-mediated cytoskeletal linkages and ligand-binding affinity [J].
Huttenlocher, A ;
Ginsberg, MH ;
Horwitz, AF .
JOURNAL OF CELL BIOLOGY, 1996, 134 (06) :1551-1562