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Volume 272, Number 40, Issue of October 3, 1997 pp. 24832-24836
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

Fibronectin Type III5 Repeat Contains a Novel Cell Adhesion Sequence, KLDAPT, Which Binds Activated alpha 4beta 1 and alpha 4beta 7 Integrins

(Received for publication, April 3, 1997, and in revised form, July 14, 1997)

José V. Moyano Dagger , Barbara Carnemolla par , Carmen Domínguez-Jiménez Dagger , Mercedes García-Gila Dagger , Juan P. Albar §§ , Paloma Sánchez-Aparicio Dagger , Alessandra Leprini par , Germano Querzé par , Luciano Zardi par and Angeles Garcia-Pardo Dagger

From the Dagger  Departamento de Inmunología, Centro de Investigaciones Biológicas, CSIC, 28006 Madrid, Spain; par  Laboratory of Cell Biology, Istituto Nazionale per la Ricerca sul Cancro, 16132 Genoa, Italy; and §§ Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología, CSIC, 28049 Madrid, Spain

The region of fibronectin encompassing type III repeats 4-6 contains a low affinity heparin binding domain, but its physiological significance is not clear. We have studied whether this domain is able to interact with cells as already shown for other heparin binding domains of fibronectin. A computer search based on homologies with known active sites in fibronectin revealed the sequence KLDAPT located in FN-III5. A synthetic peptide containing this sequence induced lymphoid cell adhesion upon treatment with the activating anti-beta 1 monoclonal antibody (mAb) TS2/16 or with Mn2+, indicating that KLDAPT was binding to an integrin. A recombinant fragment containing repeat III5 (FN-III5) also mediated adhesion of TS2/16/Mn2+-treated cells while the FN-III6 fragment did not. Soluble KLDAPT peptide inhibited cell adhesion to FN-III5 as well as to a 38-kDa fibronectin fragment and VCAM-1, two previously known ligands for alpha 4beta 1 integrin. KLDAPT also competed with the binding of soluble alkaline phosphatase-coupled VCAM-Ig to Mn2+-treated alpha 4beta 1. Furthermore, mAbs anti-alpha 4 and anti-alpha 4beta 7, but not mAbs to other integrins, inhibited cell adhesion to FN-III5 and KLDAPT. These results therefore establish a cell adhesive function for the FN-III5 repeat and show that KLDAPT is a novel fibronectin ligand for activated alpha 4 integrins.


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Copyright © 1997 by the American Society for Biochemistry and Molecular Biology.