Linked Life Data

8486666

Source:http://linkedlifedata.com/resource/pubmed/id/8486666

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
1993-6-4
pubmed:abstractText
The VLA integrin subfamily includes receptors for extracellular matrix proteins as well as receptors involved in cell-cell adhesive interactions. We have previously described the up-regulation of VLA integrin-mediated cell attachment to different ligands by the anti-beta 1 TS2/16 monoclonal antibody (mAb) (Arroyo, A. G., Sánchez-Mateos, P., Campanero, M. R., Martín-Padura, I., Dejana, E., and Sánchez-Madrid, F. (1992) J. Cell Biol. 117, 659-670). In this report, we have investigated the mechanism involved in this regulatory effect. The anti-beta 1-mediated regulatory effect on cell adhesion did not require "de novo" protein synthesis, since it was not affected by pretreatment with either cycloheximide or actinomycin D. To quantitate the effect of the regulatory anti-beta 1 TS2/16 mAb on the affinity of VLA-5 for its ligand, an RGD-containing fragment of fibronectin (FN80), we performed binding studies of radiolabeled soluble FN80 to U-937 cells. The affinity of VLA-5 for FN80 was enhanced about 4-fold in the presence of TS2/16 mAb (Kd = 0.98 +/- 0.07 microM) compared to the functionally irrelevant anti-beta 1 Alex 1/4 mAb (Kd = 4.23 +/- 0.92 microM), whereas no alteration in the number of binding sites was observed. Indeed, the anti-beta 1 TS2/16 mAb is inducing this high affinity state on VLA heterodimers by a direct change on the conformation of these receptors as demonstrated by affinity chromatography analysis using extracellular matrix proteins covalently bound to Sepharose. The yield of VLA-5 fibronectin receptor bound to FN80-Sepharose columns was strongly increased upon treatment of U-937 cell lysates with mAb TS2/16. Moreover, higher concentrations of EDTA were required for eluting the VLA-5 integrin from this matrix. This up-regulatory effect was also observed with F(ab')2 and Fab fragments of the anti-beta 1 TS2/16 mAb, and was also exerted on the purified VLA-5 receptor. Similarly, the yield of VLA-2 retained on a collagen I-Sepharose column was dramatically increased by pretreatment of A375 melanoma cell lysates with the mAb TS2/16. Altogether, these results indicate that the interaction of VLA beta 1 heterodimers with their ligands can be regulated by switching between differently active conformations inherent to the alpha beta 1 receptors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
268
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9863-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
A high affinity conformational state on VLA integrin heterodimers induced by an anti-beta 1 chain monoclonal antibody.
pubmed:affiliation
Hospital de la Princesa, Universidad Autónoma de Madrid, Madrid, Spain.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't