αVβ6 is a novel receptor for human fibrillin-1 -: Comparative studies of molecular determinants underlying integrin-RGD affinityand specificity

被引:65
作者
Jovanovic, Jelena
Takagi, Junichi
Choulier, Laurence
Abrescia, Nicola G. A.
Stuart, David I.
van der Merwe, P. Anton
Mardon, Helen J.
Handford, Penny A.
机构
[1] Univ Oxford, Dept Biochem, Oxford OX1 3QU, England
[2] John Radcliffe Hosp, Nuffield Dept Obstet & Gynaecol, Div Med Sci, Oxford OX3 9DU, England
[3] Henry Wellcome Bldg Genom Med, Oxford OX3 7BN, England
[4] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England
[5] Osaka Univ, Inst Prot Res, Suita, Osaka 565087, Japan
基金
英国医学研究理事会; 英国惠康基金;
关键词
D O I
10.1074/jbc.M607008200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Human fibrillin-1, the major structural protein of connective tissue 10-12 nm microfibrils, contains multiple calcium binding epidermal growth factor-like domains interspersed with transforming growth factor beta-binding protein-like (TB) domains. TB4 contains a flexible RGD loop that mediates cell adhesion via alpha V beta 3 and alpha 5 beta 1 integrins. This study identifies integrin alpha V beta 6 as a novel cellular receptor for fibrillin-1 with a K-d of similar to 0.45 mu M. Analyses of this interaction by surface plasmon resonance and immunocytochemistry reveal different module requirements for alpha V beta 6 activation compared with those of alpha V beta 3, suggesting that a covalent linkage of an N-terminal calcium binding epidermal growth factor-like domain to TB4 can modulate alpha V integrin binding specificity. Furthermore, our data suggest alpha 5 beta 1 is a low affinity fibrillin-1 receptor (K-d > 1 mu M), thus providing a molecular explanation for the different alpha 5 beta 1 distribution patterns seen when human keratinocytes and fibroblasts are plated on recombinant fibrillin fragments versus those derived from the physiological ligand fibronectin. Non-focal contact distribution of alpha 5 beta 1 suggests that its engagement by fibrillin-1 may elicit a lesser degree and/or different type of intracellular signaling compared with that seen with a high affinity ligand.
引用
收藏
页码:6743 / 6751
页数:9
相关论文
共 34 条
[1]   Synergistic activity of the ninth and tenth FIII domains of human fibronectin depends upon structural stability [J].
Altroff, H ;
Choulier, L ;
Mardon, HJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (01) :491-497
[2]   Cell adhesion to fibrillin-1 molecules and microfibrils is mediated by α5β1 and αvβ3 integrins [J].
Bax, DV ;
Bernard, SE ;
Lomas, A ;
Morgan, A ;
Humphries, J ;
Shuttleworth, CA ;
Humphries, MJ ;
Kielty, CM .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (36) :34605-34616
[3]   Distinct structural requirements for interaction of the integrins alpha 5 beta 1, alpha nu beta 5, and alpha nu beta 6 with the central cell binding domain in fibronectin [J].
Chen, J ;
Maeda, T ;
Sekiguchi, K ;
Sheppard, D .
CELL ADHESION AND COMMUNICATION, 1996, 4 (4-5) :237-250
[4]   TGF-β1 binding protein-like modules of fibrillin-1 and -2 mediate integrin-dependent cell adhesion [J].
D'Arrigo, C ;
Burl, S ;
Withers, AP ;
Dobson, H ;
Black, C ;
Boxer, M .
CONNECTIVE TISSUE RESEARCH, 1998, 37 (1-2) :29-52
[5]  
DAVIS EC, 1993, TISSUE ENGINEERING, P26
[6]   Assembly of epithelial cell fibrillins [J].
Dzamba, BJ ;
Keene, DR ;
Isogai, Z ;
Charbonneau, NL ;
Karaman-Jurukovska, N ;
Simon, M ;
Sakai, LY .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2001, 117 (06) :1612-1620
[7]  
Huang XZ, 1998, J CELL SCI, V111, P2189
[8]  
HUGHES PE, 1993, J BIOL CHEM, V268, P17727
[9]   Using model substrates to study the dependence of focal adhesion formation on the affinity of integrin-ligand complexes [J].
Kato, M ;
Mrksich, M .
BIOCHEMISTRY, 2004, 43 (10) :2699-2707
[10]   alpha V integrins on HT-29 colon carcinoma cells: Adhesion to fibronectin is mediated solely by small amounts of alpha V beta 6, and alpha V beta 5 is codistributed with actin fibers [J].
Kemperman, H ;
Wijnands, YM ;
Roos, E .
EXPERIMENTAL CELL RESEARCH, 1997, 234 (01) :156-164