Subcellular domain-dependent molecular hierarchy of SFK and FAK in mechanotransduction and cytokine signaling

Abstract Focal adhesion kinase (FAK) and Src family kinases (SFK) are known to play critical roles in mechanotransduction and other crucial cell functions. Recent reports indicate that they reside in different microdomains of the plasma membrane. However, little is known about their subcellular doma...

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Autores principales:	Qiaoqiao Wan, ThucNhi TruongVo, Hannah E. Steele, Altug Ozcelikkale, Bumsoo Han, Yingxiao Wang, Junghwan Oh, Hiroki Yokota, Sungsoo Na
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/274b50d63ae34fbeaf40c7a65fcaa9d5
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spelling	oai:doaj.org-article:274b50d63ae34fbeaf40c7a65fcaa9d52021-12-02T11:41:21ZSubcellular domain-dependent molecular hierarchy of SFK and FAK in mechanotransduction and cytokine signaling10.1038/s41598-017-09495-52045-2322https://doaj.org/article/274b50d63ae34fbeaf40c7a65fcaa9d52017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09495-5https://doaj.org/toc/2045-2322Abstract Focal adhesion kinase (FAK) and Src family kinases (SFK) are known to play critical roles in mechanotransduction and other crucial cell functions. Recent reports indicate that they reside in different microdomains of the plasma membrane. However, little is known about their subcellular domain-dependent roles and responses to extracellular stimuli. Here, we employed fluorescence resonance energy transfer (FRET)-based biosensors in conjunction with collagen-coupled agarose gels to detect subcellular activities of SFK and FAK in three-dimensional (3D) settings. We observed that SFK and FAK in the lipid rafts and nonrafts are differently regulated by fluid flow and pro-inflammatory cytokines. Inhibition of FAK in the lipid rafts blocked SFK response to fluid flow, while inhibition of SFK in the non-rafts blocked FAK activation by the cytokines. Ex-vivo FRET imaging of mouse cartilage explants showed that intermediate level of interstitial fluid flow selectively decreased cytokine-induced SFK/FAK activation. These findings suggest that SFK and FAK exert distinctive molecular hierarchy depending on their subcellular location and extracellular stimuli.Qiaoqiao WanThucNhi TruongVoHannah E. SteeleAltug OzcelikkaleBumsoo HanYingxiao WangJunghwan OhHiroki YokotaSungsoo NaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Qiaoqiao Wan ThucNhi TruongVo Hannah E. Steele Altug Ozcelikkale Bumsoo Han Yingxiao Wang Junghwan Oh Hiroki Yokota Sungsoo Na Subcellular domain-dependent molecular hierarchy of SFK and FAK in mechanotransduction and cytokine signaling
description	Abstract Focal adhesion kinase (FAK) and Src family kinases (SFK) are known to play critical roles in mechanotransduction and other crucial cell functions. Recent reports indicate that they reside in different microdomains of the plasma membrane. However, little is known about their subcellular domain-dependent roles and responses to extracellular stimuli. Here, we employed fluorescence resonance energy transfer (FRET)-based biosensors in conjunction with collagen-coupled agarose gels to detect subcellular activities of SFK and FAK in three-dimensional (3D) settings. We observed that SFK and FAK in the lipid rafts and nonrafts are differently regulated by fluid flow and pro-inflammatory cytokines. Inhibition of FAK in the lipid rafts blocked SFK response to fluid flow, while inhibition of SFK in the non-rafts blocked FAK activation by the cytokines. Ex-vivo FRET imaging of mouse cartilage explants showed that intermediate level of interstitial fluid flow selectively decreased cytokine-induced SFK/FAK activation. These findings suggest that SFK and FAK exert distinctive molecular hierarchy depending on their subcellular location and extracellular stimuli.
format	article
author	Qiaoqiao Wan ThucNhi TruongVo Hannah E. Steele Altug Ozcelikkale Bumsoo Han Yingxiao Wang Junghwan Oh Hiroki Yokota Sungsoo Na
author_facet	Qiaoqiao Wan ThucNhi TruongVo Hannah E. Steele Altug Ozcelikkale Bumsoo Han Yingxiao Wang Junghwan Oh Hiroki Yokota Sungsoo Na
author_sort	Qiaoqiao Wan
title	Subcellular domain-dependent molecular hierarchy of SFK and FAK in mechanotransduction and cytokine signaling
title_short	Subcellular domain-dependent molecular hierarchy of SFK and FAK in mechanotransduction and cytokine signaling
title_full	Subcellular domain-dependent molecular hierarchy of SFK and FAK in mechanotransduction and cytokine signaling
title_fullStr	Subcellular domain-dependent molecular hierarchy of SFK and FAK in mechanotransduction and cytokine signaling
title_full_unstemmed	Subcellular domain-dependent molecular hierarchy of SFK and FAK in mechanotransduction and cytokine signaling
title_sort	subcellular domain-dependent molecular hierarchy of sfk and fak in mechanotransduction and cytokine signaling
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/274b50d63ae34fbeaf40c7a65fcaa9d5
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Subcellular domain-dependent molecular hierarchy of SFK and FAK in mechanotransduction and cytokine signaling

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