Fibronectin type III5 repeat contains a novel cell adhesion sequence, KLDAPT, which binds activated α4β1 and α4β7 integrins

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

Research output: Contribution to journalArticle

Abstract

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-β1 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 α4β1 integrin. KLDAPT also competed with the binding of soluble alkaline phosphatase-coupled VCAM-Ig to Mn2+-treated α4β1. Furthermore, mAbs anti-α4 and anti-α4β7, 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 α4 integrins.

Original languageEnglish
Pages (from-to)24832-24836
Number of pages5
JournalJournal of Biological Chemistry
Volume272
Issue number40
DOIs
Publication statusPublished - Oct 3 1997

ASJC Scopus subject areas

  • Biochemistry

Fingerprint Dive into the research topics of 'Fibronectin type III5 repeat contains a novel cell adhesion sequence, KLDAPT, which binds activated α4β1 and α4β7 integrins'. Together they form a unique fingerprint.

  • Cite this

    Moyano, J. V., Carnemolla, B., Domínguez-Jiménez, C., García-Gila, M., Albar, J. P., Sánchez-Aparicio, P., Leprini, A., Querzé, G., Zardi, L., & Garcia-Pardo, A. (1997). Fibronectin type III5 repeat contains a novel cell adhesion sequence, KLDAPT, which binds activated α4β1 and α4β7 integrins. Journal of Biological Chemistry, 272(40), 24832-24836. https://doi.org/10.1074/jbc.272.40.24832