Extracellular matrix promotes clathrin-dependent endocytosis of prolactin and STAT5 activation in differentiating mammary epithelial cells

Abstract The hormone prolactin promotes lactational differentiation of mammary epithelial cells (MECs) via its cognate receptor and the downstream JAK2-STAT5a signalling pathway. In turn this regulates transcription of milk protein genes. Prolactin signalling depends on a cross-talk with basement me...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Rebecca E. Bridgewater, Charles H. Streuli, Patrick T. Caswell
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5e809f6f93f84d18b076c521e6b8c0a6
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:5e809f6f93f84d18b076c521e6b8c0a6
record_format	dspace
spelling	oai:doaj.org-article:5e809f6f93f84d18b076c521e6b8c0a62021-12-02T11:52:31ZExtracellular matrix promotes clathrin-dependent endocytosis of prolactin and STAT5 activation in differentiating mammary epithelial cells10.1038/s41598-017-04783-62045-2322https://doaj.org/article/5e809f6f93f84d18b076c521e6b8c0a62017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04783-6https://doaj.org/toc/2045-2322Abstract The hormone prolactin promotes lactational differentiation of mammary epithelial cells (MECs) via its cognate receptor and the downstream JAK2-STAT5a signalling pathway. In turn this regulates transcription of milk protein genes. Prolactin signalling depends on a cross-talk with basement membrane extracellular matrix (ECM) via β1 integrins which activate both ILK and Rac1 and are required for STAT5a activation and lactational differentiation. Endocytosis is an important regulator of signalling. It can both enhance and suppress cytokine signalling, although the role of endocytosis for prolactin signalling is not known. Here we show that clathrin-mediated endocytosis is required for ECM-dependent STAT5 activation. In the presence of ECM, prolactin is internalised via a clathrin-dependent, but caveolin-independent, route. This occurs independently from JAK2 and Rac signalling, but is required for full phosphorylation and activation of STAT5. Prolactin is internalised into early endosomes, where the master early endosome regulator Rab5b promotes STAT5 phosphorylation. These data reveal a novel role for ECM-driven endocytosis in the positive regulation of cytokine signalling.Rebecca E. BridgewaterCharles H. StreuliPatrick T. CaswellNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rebecca E. Bridgewater Charles H. Streuli Patrick T. Caswell Extracellular matrix promotes clathrin-dependent endocytosis of prolactin and STAT5 activation in differentiating mammary epithelial cells
description	Abstract The hormone prolactin promotes lactational differentiation of mammary epithelial cells (MECs) via its cognate receptor and the downstream JAK2-STAT5a signalling pathway. In turn this regulates transcription of milk protein genes. Prolactin signalling depends on a cross-talk with basement membrane extracellular matrix (ECM) via β1 integrins which activate both ILK and Rac1 and are required for STAT5a activation and lactational differentiation. Endocytosis is an important regulator of signalling. It can both enhance and suppress cytokine signalling, although the role of endocytosis for prolactin signalling is not known. Here we show that clathrin-mediated endocytosis is required for ECM-dependent STAT5 activation. In the presence of ECM, prolactin is internalised via a clathrin-dependent, but caveolin-independent, route. This occurs independently from JAK2 and Rac signalling, but is required for full phosphorylation and activation of STAT5. Prolactin is internalised into early endosomes, where the master early endosome regulator Rab5b promotes STAT5 phosphorylation. These data reveal a novel role for ECM-driven endocytosis in the positive regulation of cytokine signalling.
format	article
author	Rebecca E. Bridgewater Charles H. Streuli Patrick T. Caswell
author_facet	Rebecca E. Bridgewater Charles H. Streuli Patrick T. Caswell
author_sort	Rebecca E. Bridgewater
title	Extracellular matrix promotes clathrin-dependent endocytosis of prolactin and STAT5 activation in differentiating mammary epithelial cells
title_short	Extracellular matrix promotes clathrin-dependent endocytosis of prolactin and STAT5 activation in differentiating mammary epithelial cells
title_full	Extracellular matrix promotes clathrin-dependent endocytosis of prolactin and STAT5 activation in differentiating mammary epithelial cells
title_fullStr	Extracellular matrix promotes clathrin-dependent endocytosis of prolactin and STAT5 activation in differentiating mammary epithelial cells
title_full_unstemmed	Extracellular matrix promotes clathrin-dependent endocytosis of prolactin and STAT5 activation in differentiating mammary epithelial cells
title_sort	extracellular matrix promotes clathrin-dependent endocytosis of prolactin and stat5 activation in differentiating mammary epithelial cells
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/5e809f6f93f84d18b076c521e6b8c0a6
work_keys_str_mv	AT rebeccaebridgewater extracellularmatrixpromotesclathrindependentendocytosisofprolactinandstat5activationindifferentiatingmammaryepithelialcells AT charleshstreuli extracellularmatrixpromotesclathrindependentendocytosisofprolactinandstat5activationindifferentiatingmammaryepithelialcells AT patricktcaswell extracellularmatrixpromotesclathrindependentendocytosisofprolactinandstat5activationindifferentiatingmammaryepithelialcells
_version_	1718394987615354880

Extracellular matrix promotes clathrin-dependent endocytosis of prolactin and STAT5 activation in differentiating mammary epithelial cells

Ejemplares similares