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PMID: 8458867 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Affinity modulation of integrin alpha 5 beta 1: regulation of the functional response by soluble fibronectin.

The Journal of cell biology ·Vol. 121 ·No. 1 ·1993-04-00 ·Pages 155-62

Faull RJ, Kovach NL, Harlan JM, Ginsberg MH

Abstract

We report that a beta 1 integrin (alpha 5 beta 1) can exist in different affinity states for its soluble ligand, fibronectin. The alpha 5 beta 1 expressed by the erythroleukemic cell line K562 binds soluble fibronectin with low affinity (Kd > 1 microM), but is induced to bind it with 20-fold higher affinity (Kd-54 nM) in the presence of the anti-beta 1 mAb 8A2. This activation seems to be due to direct antibody-induced change in the receptor that does not require intracellular signaling, and is a plausible basis for the 8A2-induced enhancement of beta 1-dependent adhesion to fibronectin and other immobilized ligands (Kovach, N. L., T. M. Carlos, E. Yee, and J. M. Harlan. 1992. J. Cell Biol. 116: 499-509). Fab fragments of 8A2 bind with higher affinity to alpha 5 beta 1 receptor that is occupied by the GRG-DSP peptide ligand suggesting that the antibody functions by stabilizing a high affinity (occupied) conformer of the receptor. A functional consequence of the affinity modulation is that soluble fibronectin (at physiological concentrations) occupies the high affinity receptors, and so becomes an effective inhibitor of adhesion to immobilized fibronectin. In contrast, the majority of low affinity receptors remain unoccupied and are still to mediate cellular adhesion.

MeSH Terms
Animals Antibodies, Monoclonal Cell Adhesion Cells, Cultured Fibronectins/metabolism Humans Mice Protein Conformation Rats Receptors, Fibronectin/metabolism Solubility T-Lymphocytes/cytology Tumor Cells, Cultured
Chemicals
Antibodies, Monoclonal Fibronectins Receptors, Fibronectin
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Faull R J
Scripps Research Institute, La Jolla, California 92037.
Kovach N L
Harlan J M
Ginsberg M H
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.121.1.155
Published
1993-04-00
Pages
155-62
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2119780
Subset
IM
Grants
NIAMS NIH HHS · AR 27214 · United States
NHLBI NIH HHS · HL 28235 · United States
NHLBI NIH HHS · HL 487281 · United States
External Links
PubMed source DOI: 10.1083/jcb.121.1.155 PMC Full Text View journal details
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