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Multiple functional forms of the integrin VLA-2 can be derived from a single alpha 2 cDNA clone: interconversion of forms induced by an anti- beta 1 antibody
The integrin VLA-2 was previously found to bind to either collagen alone, or collagen plus laminin, but the mechanism for this cell- specific functional difference was unknown. Here we transfected VLA-2 alpha 2 subunit cDNA into K562 cells and obtained VLA-2 (called Form-O) which bound to neither co...
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Lenguaje: | English |
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The Rockefeller University Press
1993
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2119525/ https://www.ncbi.nlm.nih.gov/pubmed/8421065 |
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collection | PubMed |
description | The integrin VLA-2 was previously found to bind to either collagen alone, or collagen plus laminin, but the mechanism for this cell- specific functional difference was unknown. Here we transfected VLA-2 alpha 2 subunit cDNA into K562 cells and obtained VLA-2 (called Form-O) which bound to neither collagen nor laminin. We then used a Matrigel selection procedure to enrich for a minor subpopulation of K562 cells stably expressing a form of VLA-2 (Form-C) that bound to collagen but not laminin. In contrast, the same alpha 2 cDNA transfected into RD cells yielded VLA-2 (Form-CL) which bound to both collagen and laminin. These Form-O, -C, and -CL activities were stably expressed during extended cell culture, and could not be qualitatively altered by adding phorbol esters or by exchaning the resident divalent cations. However, addition of stimulatory anti-beta 1 antibodies (TS2/16, A-1A5) rapidly converted VLA-2 Form-O and Form-C into Form-CL. Anti-beta 1 antibody stimulation of VLA-2 activity was observed not only on whole cells, but also with solubilized receptors. These results suggest (a) that the ligand binding specificity of VLA-2 can be determined by its cellular environment, rather than by variations in the primary sequence of the alpha 2 subunit, (b) that stably inactive or partly active VLA-2 can be rapidly converted to a fully active form through conformational changes initiated at a nonligand binding site on the beta 1 subunit, and (c) that the mechanisms for VLA-2 stimulation by phorbol ester and by antibody are quite distinct, because the latter does not require an intact cell. |
format | Text |
id | pubmed-2119525 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1993 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21195252008-05-01 Multiple functional forms of the integrin VLA-2 can be derived from a single alpha 2 cDNA clone: interconversion of forms induced by an anti- beta 1 antibody J Cell Biol Articles The integrin VLA-2 was previously found to bind to either collagen alone, or collagen plus laminin, but the mechanism for this cell- specific functional difference was unknown. Here we transfected VLA-2 alpha 2 subunit cDNA into K562 cells and obtained VLA-2 (called Form-O) which bound to neither collagen nor laminin. We then used a Matrigel selection procedure to enrich for a minor subpopulation of K562 cells stably expressing a form of VLA-2 (Form-C) that bound to collagen but not laminin. In contrast, the same alpha 2 cDNA transfected into RD cells yielded VLA-2 (Form-CL) which bound to both collagen and laminin. These Form-O, -C, and -CL activities were stably expressed during extended cell culture, and could not be qualitatively altered by adding phorbol esters or by exchaning the resident divalent cations. However, addition of stimulatory anti-beta 1 antibodies (TS2/16, A-1A5) rapidly converted VLA-2 Form-O and Form-C into Form-CL. Anti-beta 1 antibody stimulation of VLA-2 activity was observed not only on whole cells, but also with solubilized receptors. These results suggest (a) that the ligand binding specificity of VLA-2 can be determined by its cellular environment, rather than by variations in the primary sequence of the alpha 2 subunit, (b) that stably inactive or partly active VLA-2 can be rapidly converted to a fully active form through conformational changes initiated at a nonligand binding site on the beta 1 subunit, and (c) that the mechanisms for VLA-2 stimulation by phorbol ester and by antibody are quite distinct, because the latter does not require an intact cell. The Rockefeller University Press 1993-01-02 /pmc/articles/PMC2119525/ /pubmed/8421065 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Articles Multiple functional forms of the integrin VLA-2 can be derived from a single alpha 2 cDNA clone: interconversion of forms induced by an anti- beta 1 antibody |
title | Multiple functional forms of the integrin VLA-2 can be derived from a single alpha 2 cDNA clone: interconversion of forms induced by an anti- beta 1 antibody |
title_full | Multiple functional forms of the integrin VLA-2 can be derived from a single alpha 2 cDNA clone: interconversion of forms induced by an anti- beta 1 antibody |
title_fullStr | Multiple functional forms of the integrin VLA-2 can be derived from a single alpha 2 cDNA clone: interconversion of forms induced by an anti- beta 1 antibody |
title_full_unstemmed | Multiple functional forms of the integrin VLA-2 can be derived from a single alpha 2 cDNA clone: interconversion of forms induced by an anti- beta 1 antibody |
title_short | Multiple functional forms of the integrin VLA-2 can be derived from a single alpha 2 cDNA clone: interconversion of forms induced by an anti- beta 1 antibody |
title_sort | multiple functional forms of the integrin vla-2 can be derived from a single alpha 2 cdna clone: interconversion of forms induced by an anti- beta 1 antibody |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2119525/ https://www.ncbi.nlm.nih.gov/pubmed/8421065 |