Hemophilic interaction of junctional adhesion molecule

被引:125
作者
Bazzoni, G
Martìnez-Estrada, OM
Mueller, F
Nelboeck, P
Schmid, G
Bartfai, T
Dejana, E
Brockhaus, M
机构
[1] Ist Ric Farmacol Mario Negri, Lab Vasc Biol, I-20157 Milan, Italy
[2] F Hoffmann La Roche & Co Ltd, Pharmaceut Res, CH-4070 Basel, Switzerland
[3] F Hoffmann La Roche & Co Ltd, Chem Technol, CH-4070 Basel, Switzerland
[4] F Hoffmann La Roche & Co Ltd, Cent Nervous Syst Dis, CH-4070 Basel, Switzerland
[5] F Hoffmann La Roche & Co Ltd, Fermentat Technol, CH-4070 Basel, Switzerland
[6] Univ Insubria, Dipartimento Sci Clin & Biol, I-21100 Varese, Italy
关键词
D O I
10.1074/jbc.M003946200
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
Junctional adhesion molecule (JAM) is an integral membrane protein that belongs to the immunoglobulin superfamily, localizes at tight junctions, and regulates both paracellular permeability and leukocyte transmigration. To investigate molecular determinants of JAM function, the extracellular domain of murine JAM was produced as a recombinant soluble protein (rsJAM) in insect cells, rsJAM consisted in large part of noncovalent homodimers, as assessed by analytical ultracentrifugation, JAM dimers were also detected at the surface of Chinese hamster ovary cells transfected with murine JAM, as evaluated by cross-linking and immunoprecipitation. Furthermore, fluid-phase rsJAM bound dose-dependently solid-phase rsJAM, and such hemophilic binding was inhibited by anti-JAM Fab BV11, but not by Fab BV12, Interestingly, Fab BV11 exclusively bound rsJAM dimers (but not monomers) in solution, whereas Fab BV12 bound both dimers and monomers, Finally, we mapped the BV11 and BV12 epitopes to a largely overlapping sequence in proximity of the extracellular amino terminus of JAM, me hypothesize that rsJAM dimerization induces a BV11-positive conformation which in turn is critical for rsJAM hemophilic interactions. Dimerization and hemophilic binding may contribute to both adhesive function and junctional organization of JAM.
引用
收藏
页码:30970 / 30976
页数:7
相关论文
共 31 条
[1]   Are changes in integrin affinity and conformation overemphasized? [J].
Bazzoni, G ;
Hemler, ME .
TRENDS IN BIOCHEMICAL SCIENCES, 1998, 23 (01) :30-34
[2]  
BEDNARCZYK JL, 1994, J BIOL CHEM, V269, P8348
[3]   Lateral dimerization is required for the homophilic binding activity of C-cadherin [J].
Brieher, WM ;
Yap, AS ;
Gumbiner, BM .
JOURNAL OF CELL BIOLOGY, 1996, 135 (02) :487-496
[4]   A dimeric crystal structure for the N-terminal two domains of intercellular adhesion molecule-1 [J].
Casasnovas, JM ;
Stehle, T ;
Liu, JH ;
Wang, JH ;
Springer, TA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (08) :4134-4139
[5]   The molecular structure of cell adhesion molecules [J].
Chothia, C ;
Jones, EY .
ANNUAL REVIEW OF BIOCHEMISTRY, 1997, 66 :823-862
[6]   Leukocyte recruitment in the cerebrospinal fluid of mice with experimental meningitis is inhibited by an antibody to junctional adhesion molecule (JAM) [J].
Del Maschio, A ;
De Luigi, A ;
Martin-Padura, I ;
Brockhaus, M ;
Bartfai, T ;
Fruscella, P ;
Adorini, L ;
Martino, GV ;
Furlan, R ;
De Simoni, MG ;
Dejana, E .
JOURNAL OF EXPERIMENTAL MEDICINE, 1999, 190 (09) :1351-1356
[7]   Visualization of CD2 interaction with LFA-3 and determination of the two-dimensional dissociation constant for adhesion receptors in a contact area [J].
Dustin, ML ;
Ferguson, LM ;
Chan, PY ;
Springer, TA ;
Golan, DE .
JOURNAL OF CELL BIOLOGY, 1996, 132 (03) :465-474
[8]  
FRELINGER AL, 1990, J BIOL CHEM, V265, P6346
[9]   TRANSGLUTAMINASES - MULTIFUNCTIONAL CROSS-LINKING ENZYMES THAT STABILIZE TISSUES [J].
GREENBERG, CS ;
BIRCKBICHLER, PJ ;
RICE, RH .
FASEB JOURNAL, 1991, 5 (15) :3071-3077
[10]   A peptide derived from a beta(2)-adrenergic receptor transmembrane domain inhibits both receptor dimerization and activation [J].
Hebert, TE ;
Moffett, S ;
Morello, JP ;
Loisel, TP ;
Bichet, DG ;
Barret, C ;
Bouvier, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (27) :16384-16392