Calzada, M. J. and Annis, D. S. and Zeng, B. X. and Marcinkiewicz, C. and Banas, Bernhard and Lawler, J. and Mosher, D. F. and Roberts, D. D. (2004) Identification of novel beta(1) integrin binding sites in the type 1 and type 2 repeats of thrombospondin-1. JOURNAL OF BIOLOGICAL CHEMISTRY, 279 (40). pp. 41734-41743. ISSN 0021-9258, 1083-351X
Full text not available from this repository. (Request a copy)Abstract
In addition to the three known beta(1) integrin recognition sites in the N-module of thrombospondin-1 (TSP1), we found that beta(1) integrins mediate cell adhesion to the type 1 and type 2 repeats. The type 1 repeats of TSP1 differ from typical integrin ligands in that recognition is pan-beta(1)-specific. Adhesion of cells that express one dominant beta(1) integrin on immobilized type 1 repeats is specifically inhibited by antagonists of that integrin, whereas adhesion of cells that express several beta(1) integrins is partially inhibited by each alpha-subunit-specific antagonist and completely inhibited by combining the antagonists. beta(1) integrins recognize both the second and third type 1 repeats, and each type 1 repeat shows pan-beta(1) specificity and divalent cation dependence for promoting cell adhesion. Adhesion to the type 2 repeats is less sensitive to alpha-subunit antagonists, but a beta(1) blocking antibody and two disintegrins inhibit adhesion to immobilized type 2 repeats. beta(1) integrin expression is necessary for cell adhesion to the type 1 or type 2 repeats, and beta(1) integrins bind in a divalent cation-dependent manner to a type 1 repeat affinity column. The widely used TSP1 function blocking antibody A4.1 binds to a site in the third type 2 repeat. A4.1 proximally inhibits beta(1) integrin-dependent adhesion to the type 2 repeats and indirectly inhibits integrin-dependent adhesion mediated by the TSP1 type 1 repeats. Although antibody A4.1 is also an antagonist of CD36 binding to TSP1, these data suggest that some biological activities of A4.1 result from antagonism of these novel beta(1) integrin binding sites.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | AMINO-ACID SUBSTITUTIONS; ARG-GLY-ASP; CELL ATTACHMENT; ALPHA-3-BETA-1 INTEGRIN; T-CELL; ALPHA(3)BETA(1) INTEGRIN; ALPHA-4-BETA-1 INTEGRIN; NEURITE OUTGROWTH; MESANGIAL CELLS; I REPEATS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II Medicine > Abteilung für Nephrologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 28 Jun 2021 05:41 |
| Last Modified: | 28 Jun 2021 05:41 |
| URI: | https://pred.uni-regensburg.de/id/eprint/37131 |
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