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Receptor tyrosine kinase Met promotes cell survival via kinase-independent maintenance of integrin α3β1

Matrix adhesion via integrins is required for cell survival. Adhesion of epithelial cells to laminin via integrin α3β1 was previously shown to activate at least two independent survival pathways. First, integrin α3β1 is required for autophagy-induced cell survival after growth factor deprivation. Se...

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Autores principales: Tesfay, Lia, Schulz, Veronique V., Frank, Sander B., Lamb, Laura E., Miranti, Cindy K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4966988/
https://www.ncbi.nlm.nih.gov/pubmed/27307589
http://dx.doi.org/10.1091/mbc.E15-09-0649
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author Tesfay, Lia
Schulz, Veronique V.
Frank, Sander B.
Lamb, Laura E.
Miranti, Cindy K.
author_facet Tesfay, Lia
Schulz, Veronique V.
Frank, Sander B.
Lamb, Laura E.
Miranti, Cindy K.
author_sort Tesfay, Lia
collection PubMed
description Matrix adhesion via integrins is required for cell survival. Adhesion of epithelial cells to laminin via integrin α3β1 was previously shown to activate at least two independent survival pathways. First, integrin α3β1 is required for autophagy-induced cell survival after growth factor deprivation. Second, integrin α3β1 independently activates two receptor tyrosine kinases, EGFR and Met, in the absence of ligands. EGFR signaling to Erk promotes survival independently of autophagy. To determine how Met promotes cell survival, we inhibited Met kinase activity or blocked its expression with RNA interference. Loss of Met expression, but not inhibition of Met kinase activity, induced apoptosis by reducing integrin α3β1 levels, activating anoikis, and blocking autophagy. Met was specifically required for the assembly of autophagosomes downstream of LC3II processing. Reexpression of wild-type Met, kinase-dead Met, or integrin α3 was sufficient to rescue death upon removal of endogenous Met. Integrin α3β1 coprecipitated and colocalized with Met in cells. The extracellular and transmembrane domain of Met was required to fully rescue cell death and restore integrin α3 expression. Thus Met promotes survival of laminin-adherent cells by maintaining integrin α3β1 via a kinase-independent mechanism.
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spelling pubmed-49669882016-10-16 Receptor tyrosine kinase Met promotes cell survival via kinase-independent maintenance of integrin α3β1 Tesfay, Lia Schulz, Veronique V. Frank, Sander B. Lamb, Laura E. Miranti, Cindy K. Mol Biol Cell Articles Matrix adhesion via integrins is required for cell survival. Adhesion of epithelial cells to laminin via integrin α3β1 was previously shown to activate at least two independent survival pathways. First, integrin α3β1 is required for autophagy-induced cell survival after growth factor deprivation. Second, integrin α3β1 independently activates two receptor tyrosine kinases, EGFR and Met, in the absence of ligands. EGFR signaling to Erk promotes survival independently of autophagy. To determine how Met promotes cell survival, we inhibited Met kinase activity or blocked its expression with RNA interference. Loss of Met expression, but not inhibition of Met kinase activity, induced apoptosis by reducing integrin α3β1 levels, activating anoikis, and blocking autophagy. Met was specifically required for the assembly of autophagosomes downstream of LC3II processing. Reexpression of wild-type Met, kinase-dead Met, or integrin α3 was sufficient to rescue death upon removal of endogenous Met. Integrin α3β1 coprecipitated and colocalized with Met in cells. The extracellular and transmembrane domain of Met was required to fully rescue cell death and restore integrin α3 expression. Thus Met promotes survival of laminin-adherent cells by maintaining integrin α3β1 via a kinase-independent mechanism. The American Society for Cell Biology 2016-08-01 /pmc/articles/PMC4966988/ /pubmed/27307589 http://dx.doi.org/10.1091/mbc.E15-09-0649 Text en © 2016 Tesfay, Schulz, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Tesfay, Lia
Schulz, Veronique V.
Frank, Sander B.
Lamb, Laura E.
Miranti, Cindy K.
Receptor tyrosine kinase Met promotes cell survival via kinase-independent maintenance of integrin α3β1
title Receptor tyrosine kinase Met promotes cell survival via kinase-independent maintenance of integrin α3β1
title_full Receptor tyrosine kinase Met promotes cell survival via kinase-independent maintenance of integrin α3β1
title_fullStr Receptor tyrosine kinase Met promotes cell survival via kinase-independent maintenance of integrin α3β1
title_full_unstemmed Receptor tyrosine kinase Met promotes cell survival via kinase-independent maintenance of integrin α3β1
title_short Receptor tyrosine kinase Met promotes cell survival via kinase-independent maintenance of integrin α3β1
title_sort receptor tyrosine kinase met promotes cell survival via kinase-independent maintenance of integrin α3β1
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4966988/
https://www.ncbi.nlm.nih.gov/pubmed/27307589
http://dx.doi.org/10.1091/mbc.E15-09-0649
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