A Molecular Mechanism of Integrin Crosstalk: α(v)β(3 )Suppression of Calcium/Calmodulin-dependent Protein Kinase II Regulates α(5)β(1) Function
Many cells express more than one integrin receptor for extracellular matrix, and in vivo these receptors may be simultaneously engaged. Ligation of one integrin may influence the behavior of others on the cell, a phenomenon we have called integrin crosstalk. Ligation of the integrin α(v)β(3) inhibit...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
1999
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2133176/ https://www.ncbi.nlm.nih.gov/pubmed/10330414 |
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author | Blystone, Scott D. Slater, Suzanne E. Williams, Matthew P. Crow, Michael T. Brown, Eric J. |
author_facet | Blystone, Scott D. Slater, Suzanne E. Williams, Matthew P. Crow, Michael T. Brown, Eric J. |
author_sort | Blystone, Scott D. |
collection | PubMed |
description | Many cells express more than one integrin receptor for extracellular matrix, and in vivo these receptors may be simultaneously engaged. Ligation of one integrin may influence the behavior of others on the cell, a phenomenon we have called integrin crosstalk. Ligation of the integrin α(v)β(3) inhibits both phagocytosis and migration mediated by α(5)β(1) on the same cell, and the β(3) cytoplasmic tail is necessary and sufficient for this regulation of α(5)β(1). Ligation of α(5)β(1) activates the calcium- and calmodulin-dependent protein kinase II (CamKII). This activation is required for α(5)β(1)-mediated phagocytosis and migration. Simultaneous ligation of α(v)β(3) or expression of a chimeric molecule with a free β(3) cytoplasmic tail prevents α(5)β(1)-mediated activation of CamKII. Expression of a constitutively active CamKII restores α(5)β(1) functions blocked by α(v)β(3)-initiated integrin crosstalk. Thus, α(v)β(3) inhibition of α(5)β(1) activation of CamKII is required for its role in integrin crosstalk. Structure-function analysis of the β(3) cytoplasmic tail demonstrates a requirement for Ser752 in β(3)-mediated suppression of CamKII activation, while crosstalk is independent of Tyr747 and Tyr759, implicating Ser752, but not β(3) tyrosine phosphorylation in initiation of the α(v)β(3) signal for integrin crosstalk. |
format | Text |
id | pubmed-2133176 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1999 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21331762008-05-01 A Molecular Mechanism of Integrin Crosstalk: α(v)β(3 )Suppression of Calcium/Calmodulin-dependent Protein Kinase II Regulates α(5)β(1) Function Blystone, Scott D. Slater, Suzanne E. Williams, Matthew P. Crow, Michael T. Brown, Eric J. J Cell Biol Regular Articles Many cells express more than one integrin receptor for extracellular matrix, and in vivo these receptors may be simultaneously engaged. Ligation of one integrin may influence the behavior of others on the cell, a phenomenon we have called integrin crosstalk. Ligation of the integrin α(v)β(3) inhibits both phagocytosis and migration mediated by α(5)β(1) on the same cell, and the β(3) cytoplasmic tail is necessary and sufficient for this regulation of α(5)β(1). Ligation of α(5)β(1) activates the calcium- and calmodulin-dependent protein kinase II (CamKII). This activation is required for α(5)β(1)-mediated phagocytosis and migration. Simultaneous ligation of α(v)β(3) or expression of a chimeric molecule with a free β(3) cytoplasmic tail prevents α(5)β(1)-mediated activation of CamKII. Expression of a constitutively active CamKII restores α(5)β(1) functions blocked by α(v)β(3)-initiated integrin crosstalk. Thus, α(v)β(3) inhibition of α(5)β(1) activation of CamKII is required for its role in integrin crosstalk. Structure-function analysis of the β(3) cytoplasmic tail demonstrates a requirement for Ser752 in β(3)-mediated suppression of CamKII activation, while crosstalk is independent of Tyr747 and Tyr759, implicating Ser752, but not β(3) tyrosine phosphorylation in initiation of the α(v)β(3) signal for integrin crosstalk. The Rockefeller University Press 1999-05-17 /pmc/articles/PMC2133176/ /pubmed/10330414 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 | Regular Articles Blystone, Scott D. Slater, Suzanne E. Williams, Matthew P. Crow, Michael T. Brown, Eric J. A Molecular Mechanism of Integrin Crosstalk: α(v)β(3 )Suppression of Calcium/Calmodulin-dependent Protein Kinase II Regulates α(5)β(1) Function |
title | A Molecular Mechanism of Integrin Crosstalk: α(v)β(3 )Suppression of Calcium/Calmodulin-dependent Protein Kinase II Regulates α(5)β(1) Function |
title_full | A Molecular Mechanism of Integrin Crosstalk: α(v)β(3 )Suppression of Calcium/Calmodulin-dependent Protein Kinase II Regulates α(5)β(1) Function |
title_fullStr | A Molecular Mechanism of Integrin Crosstalk: α(v)β(3 )Suppression of Calcium/Calmodulin-dependent Protein Kinase II Regulates α(5)β(1) Function |
title_full_unstemmed | A Molecular Mechanism of Integrin Crosstalk: α(v)β(3 )Suppression of Calcium/Calmodulin-dependent Protein Kinase II Regulates α(5)β(1) Function |
title_short | A Molecular Mechanism of Integrin Crosstalk: α(v)β(3 )Suppression of Calcium/Calmodulin-dependent Protein Kinase II Regulates α(5)β(1) Function |
title_sort | molecular mechanism of integrin crosstalk: α(v)β(3 )suppression of calcium/calmodulin-dependent protein kinase ii regulates α(5)β(1) function |
topic | Regular Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2133176/ https://www.ncbi.nlm.nih.gov/pubmed/10330414 |
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