Activation of the α4β1 Integrin through the β1 Subunit Induces Recognition of the RGDS Sequence in Fibronectin

• Published in: The Journal of cell biology 1994-07, Vol.126 (1), p.271-279
• Main Authors: Sánchez-Aparicio, Paloma, Dominguez-Jiménez, Carmen, Garcia-Pardo, Angeles
• Format: Article
• Language: English
• Subjects: B lymphocytes; Biological and medical sciences; Cell adhesion; Cell interactions, adhesion; Cell lines; Collagens; Fibrosis; Fundamental and applied biological sciences. Psychology; Integrins; Ligands; Lymphocytes; Molecular and cellular biology; Receptors; T lymphocytes
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.126.1.271

Lymphocyte attachment to fibronectin is mainly mediated by the interaction of α5β1 and α4β1 integrins with the RGD and CS-1/Hep II sites, respectively. We have recently shown that the anti-β1 mAb TS2/16 can convert the partly active α4β1 present on certain hemopoietic cells that recognizes CS-1 but not Hep II, to a high avidity form that binds both ligands. In this report we have studied whether mAb TS2/16 also affects α4β1 ligand specificity. Incubation of the B cell lines Ramos and Daudi (which lack α5β1) with mAb TS2/16 induced specific attachment to an 80-kD fragment which lacks CS-1 and Hep II and contains the RGD sequence. mAbs anti-α4 and the synthetic peptides CS-1 and IDAPS inhibited adhesion to the 80-kD fragment thus implying α4β1 as the receptor for this fragment. Interestingly, the synthetic peptide GRGDSPC and a 15-kD peptic fibronectin fragment containing the RGD sequence also inhibited B cell adhesion to the 80-kD fragment. Because we have previously shown that RGD peptides do not affect the constitutive function of α4β1, we tested whether TS2/16-activated α4β1 acquired the capacity to recognize RGD. Indeed RGD peptides inhibited TS2/16-treated B cell adhesion to a 38-kD fragment containing CS-1 and Hep II but did not affect binding of untreated cells to this fragment. An anti-fibronectin mAb reactive with an epitope on or near the RGD sequence also efficiently inhibited cell adhesion to the 80-kD fragment, indicating that the RGD sequence is a novel adhesive ligand for activated α4β1. These results emphasize the role of α4β1 as a receptor with different ligand specificities according to the activation state, a fact that may be important for lymphocyte migration, localization, and function.