PTP1B triggers integrin-mediated repression of myosin activity and modulates cell contractility

Autores
González Sánchez Wusener, Ana Elena; González, Angela; Nakamura, Fumihiko; Arregui, Carlos Oscar
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Cell contractility and migration by integrins depends on precise regulation of protein tyrosine kinase and Rho-family GTPase activities in specific spatiotemporal patterns. Here we show that protein tyrosine phosphatase PTP1B cooperates with β3 integrin to activate the Src/FAK signalling pathway which represses RhoAmyosin- dependent contractility. Using PTP1B null (KO) cells and PTP1B reconstituted (WT) cells, we determined that some early steps following cell adhesion to fibronectin and vitronectin occurred robustly in WT cells, including aggregation of β3 integrins and adaptor proteins, and activation of Src/FAK-dependent signalling at small puncta in a lamellipodium. However, these events were significantly impaired in KO cells. We established that cytoskeletal strain and cell contractility was highly enhanced at the periphery of KO cells compared to WT cells. Inhibition of the Src/FAK signalling pathway or expression of constitutive active RhoA in WT cells induced a KO cell phenotype. Conversely, expression of constitutive active Src or myosin inhibition in KO cells restored the WT phenotype.We propose that this novel function of PTP1B stimulates permissive conditions for adhesion and lamellipodium assembly at the protruding edge during cell spreading and migration.
Fil: González Sánchez Wusener, Ana Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: González, Angela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Nakamura, Fumihiko. Harvard Medical School. Department Of Medicine; Estados Unidos
Fil: Arregui, Carlos Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina
Materia
CONTRACTILITY
FAK
INTEGRIN
MYOSIN
PTP1B
SRC
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/181170
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/181170
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling PTP1B triggers integrin-mediated repression of myosin activity and modulates cell contractilityGonzález Sánchez Wusener, Ana ElenaGonzález, AngelaNakamura, FumihikoArregui, Carlos OscarCONTRACTILITYFAKINTEGRINMYOSINPTP1BSRChttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Cell contractility and migration by integrins depends on precise regulation of protein tyrosine kinase and Rho-family GTPase activities in specific spatiotemporal patterns. Here we show that protein tyrosine phosphatase PTP1B cooperates with β3 integrin to activate the Src/FAK signalling pathway which represses RhoAmyosin- dependent contractility. Using PTP1B null (KO) cells and PTP1B reconstituted (WT) cells, we determined that some early steps following cell adhesion to fibronectin and vitronectin occurred robustly in WT cells, including aggregation of β3 integrins and adaptor proteins, and activation of Src/FAK-dependent signalling at small puncta in a lamellipodium. However, these events were significantly impaired in KO cells. We established that cytoskeletal strain and cell contractility was highly enhanced at the periphery of KO cells compared to WT cells. Inhibition of the Src/FAK signalling pathway or expression of constitutive active RhoA in WT cells induced a KO cell phenotype. Conversely, expression of constitutive active Src or myosin inhibition in KO cells restored the WT phenotype.We propose that this novel function of PTP1B stimulates permissive conditions for adhesion and lamellipodium assembly at the protruding edge during cell spreading and migration.Fil: González Sánchez Wusener, Ana Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: González, Angela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Nakamura, Fumihiko. Harvard Medical School. Department Of Medicine; Estados UnidosFil: Arregui, Carlos Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaCompany of Biologists Ltd2015-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/181170González Sánchez Wusener, Ana Elena; González, Angela; Nakamura, Fumihiko; Arregui, Carlos Oscar; PTP1B triggers integrin-mediated repression of myosin activity and modulates cell contractility; Company of Biologists Ltd; Biology Open; 5; 1; 12-2015; 32-442046-6390CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.bio.biologists.orginfo:eu-repo/semantics/altIdentifier/doi/10.1242/bio.015883info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:47:12Zoai:ri.conicet.gov.ar:11336/181170instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:47:12.904CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv PTP1B triggers integrin-mediated repression of myosin activity and modulates cell contractility
title PTP1B triggers integrin-mediated repression of myosin activity and modulates cell contractility
spellingShingle PTP1B triggers integrin-mediated repression of myosin activity and modulates cell contractility
González Sánchez Wusener, Ana Elena
CONTRACTILITY
FAK
INTEGRIN
MYOSIN
PTP1B
SRC
title_short PTP1B triggers integrin-mediated repression of myosin activity and modulates cell contractility
title_full PTP1B triggers integrin-mediated repression of myosin activity and modulates cell contractility
title_fullStr PTP1B triggers integrin-mediated repression of myosin activity and modulates cell contractility
title_full_unstemmed PTP1B triggers integrin-mediated repression of myosin activity and modulates cell contractility
title_sort PTP1B triggers integrin-mediated repression of myosin activity and modulates cell contractility
dc.creator.none.fl_str_mv González Sánchez Wusener, Ana Elena
González, Angela
Nakamura, Fumihiko
Arregui, Carlos Oscar
author González Sánchez Wusener, Ana Elena
author_facet González Sánchez Wusener, Ana Elena
González, Angela
Nakamura, Fumihiko
Arregui, Carlos Oscar
author_role author
author2 González, Angela
Nakamura, Fumihiko
Arregui, Carlos Oscar
author2_role author
author
author
dc.subject.none.fl_str_mv CONTRACTILITY
FAK
INTEGRIN
MYOSIN
PTP1B
SRC
topic CONTRACTILITY
FAK
INTEGRIN
MYOSIN
PTP1B
SRC
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Cell contractility and migration by integrins depends on precise regulation of protein tyrosine kinase and Rho-family GTPase activities in specific spatiotemporal patterns. Here we show that protein tyrosine phosphatase PTP1B cooperates with β3 integrin to activate the Src/FAK signalling pathway which represses RhoAmyosin- dependent contractility. Using PTP1B null (KO) cells and PTP1B reconstituted (WT) cells, we determined that some early steps following cell adhesion to fibronectin and vitronectin occurred robustly in WT cells, including aggregation of β3 integrins and adaptor proteins, and activation of Src/FAK-dependent signalling at small puncta in a lamellipodium. However, these events were significantly impaired in KO cells. We established that cytoskeletal strain and cell contractility was highly enhanced at the periphery of KO cells compared to WT cells. Inhibition of the Src/FAK signalling pathway or expression of constitutive active RhoA in WT cells induced a KO cell phenotype. Conversely, expression of constitutive active Src or myosin inhibition in KO cells restored the WT phenotype.We propose that this novel function of PTP1B stimulates permissive conditions for adhesion and lamellipodium assembly at the protruding edge during cell spreading and migration.
Fil: González Sánchez Wusener, Ana Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: González, Angela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Nakamura, Fumihiko. Harvard Medical School. Department Of Medicine; Estados Unidos
Fil: Arregui, Carlos Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina
description Cell contractility and migration by integrins depends on precise regulation of protein tyrosine kinase and Rho-family GTPase activities in specific spatiotemporal patterns. Here we show that protein tyrosine phosphatase PTP1B cooperates with β3 integrin to activate the Src/FAK signalling pathway which represses RhoAmyosin- dependent contractility. Using PTP1B null (KO) cells and PTP1B reconstituted (WT) cells, we determined that some early steps following cell adhesion to fibronectin and vitronectin occurred robustly in WT cells, including aggregation of β3 integrins and adaptor proteins, and activation of Src/FAK-dependent signalling at small puncta in a lamellipodium. However, these events were significantly impaired in KO cells. We established that cytoskeletal strain and cell contractility was highly enhanced at the periphery of KO cells compared to WT cells. Inhibition of the Src/FAK signalling pathway or expression of constitutive active RhoA in WT cells induced a KO cell phenotype. Conversely, expression of constitutive active Src or myosin inhibition in KO cells restored the WT phenotype.We propose that this novel function of PTP1B stimulates permissive conditions for adhesion and lamellipodium assembly at the protruding edge during cell spreading and migration.
publishDate 2015
dc.date.none.fl_str_mv 2015-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/181170
González Sánchez Wusener, Ana Elena; González, Angela; Nakamura, Fumihiko; Arregui, Carlos Oscar; PTP1B triggers integrin-mediated repression of myosin activity and modulates cell contractility; Company of Biologists Ltd; Biology Open; 5; 1; 12-2015; 32-44
2046-6390
CONICET Digital
CONICET
url http://hdl.handle.net/11336/181170
identifier_str_mv González Sánchez Wusener, Ana Elena; González, Angela; Nakamura, Fumihiko; Arregui, Carlos Oscar; PTP1B triggers integrin-mediated repression of myosin activity and modulates cell contractility; Company of Biologists Ltd; Biology Open; 5; 1; 12-2015; 32-44
2046-6390
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.bio.biologists.org
info:eu-repo/semantics/altIdentifier/doi/10.1242/bio.015883
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Company of Biologists Ltd
publisher.none.fl_str_mv Company of Biologists Ltd
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1844613471003475968
score 13.070432

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