CLEC14a-HSP70-1A interaction regulates HSP70-1A-induced angiogenesis

Abstract CLEC14a (C-type lectin domain family 14 member) is a tumor endothelial cell marker protein that is known to play an important role in tumor angiogenesis, but the basic molecular mechanisms underlying this function have not yet been clearly elucidated. In this study, using various proteomic...

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Autores principales:	Jihye Jang, Mi Ra Kim, Taek-Keun Kim, Woo Ran Lee, Jong Heon Kim, Kyun Heo, Sukmook Lee
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a172aad4b1524006b50e6401ef327d22
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spelling	oai:doaj.org-article:a172aad4b1524006b50e6401ef327d222021-12-02T15:06:18ZCLEC14a-HSP70-1A interaction regulates HSP70-1A-induced angiogenesis10.1038/s41598-017-11118-y2045-2322https://doaj.org/article/a172aad4b1524006b50e6401ef327d222017-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-11118-yhttps://doaj.org/toc/2045-2322Abstract CLEC14a (C-type lectin domain family 14 member) is a tumor endothelial cell marker protein that is known to play an important role in tumor angiogenesis, but the basic molecular mechanisms underlying this function have not yet been clearly elucidated. In this study, using various proteomic tools, we isolated a 70-kDa protein that interacts with the C-type lectin-like domain of CLEC14a (CLEC14a-CTLD) and identified it as heat shock protein 70-1A (HSP70-1A). Co-immunoprecipitation showed that HSP70-1A and CLEC14a interact on endothelial cells. In vitro binding analyses identified that HSP70-1A specifically associates with the region between amino acids 43 and 69 of CLEC14a-CTLD. Competitive blocking experiments indicated that this interacting region of CLEC14a-CTLD significantly inhibits HSP70-1A-induced extracellular signal-regulated kinase (ERK) phosphorylation and endothelial tube formation by directly inhibiting CLEC14a-CTLD-mediated endothelial cell-cell contacts. Our data suggest that the specific interaction of HSP70-1A with CLEC14a may play a critical role in HSP70-1A-induced angiogenesis and that the HSP70-1A-interacting region of CLEC14a-CTLD may be a useful tool for inhibiting HSP70-1A-induced angiogenesis.Jihye JangMi Ra KimTaek-Keun KimWoo Ran LeeJong Heon KimKyun HeoSukmook LeeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jihye Jang Mi Ra Kim Taek-Keun Kim Woo Ran Lee Jong Heon Kim Kyun Heo Sukmook Lee CLEC14a-HSP70-1A interaction regulates HSP70-1A-induced angiogenesis
description	Abstract CLEC14a (C-type lectin domain family 14 member) is a tumor endothelial cell marker protein that is known to play an important role in tumor angiogenesis, but the basic molecular mechanisms underlying this function have not yet been clearly elucidated. In this study, using various proteomic tools, we isolated a 70-kDa protein that interacts with the C-type lectin-like domain of CLEC14a (CLEC14a-CTLD) and identified it as heat shock protein 70-1A (HSP70-1A). Co-immunoprecipitation showed that HSP70-1A and CLEC14a interact on endothelial cells. In vitro binding analyses identified that HSP70-1A specifically associates with the region between amino acids 43 and 69 of CLEC14a-CTLD. Competitive blocking experiments indicated that this interacting region of CLEC14a-CTLD significantly inhibits HSP70-1A-induced extracellular signal-regulated kinase (ERK) phosphorylation and endothelial tube formation by directly inhibiting CLEC14a-CTLD-mediated endothelial cell-cell contacts. Our data suggest that the specific interaction of HSP70-1A with CLEC14a may play a critical role in HSP70-1A-induced angiogenesis and that the HSP70-1A-interacting region of CLEC14a-CTLD may be a useful tool for inhibiting HSP70-1A-induced angiogenesis.
format	article
author	Jihye Jang Mi Ra Kim Taek-Keun Kim Woo Ran Lee Jong Heon Kim Kyun Heo Sukmook Lee
author_facet	Jihye Jang Mi Ra Kim Taek-Keun Kim Woo Ran Lee Jong Heon Kim Kyun Heo Sukmook Lee
author_sort	Jihye Jang
title	CLEC14a-HSP70-1A interaction regulates HSP70-1A-induced angiogenesis
title_short	CLEC14a-HSP70-1A interaction regulates HSP70-1A-induced angiogenesis
title_full	CLEC14a-HSP70-1A interaction regulates HSP70-1A-induced angiogenesis
title_fullStr	CLEC14a-HSP70-1A interaction regulates HSP70-1A-induced angiogenesis
title_full_unstemmed	CLEC14a-HSP70-1A interaction regulates HSP70-1A-induced angiogenesis
title_sort	clec14a-hsp70-1a interaction regulates hsp70-1a-induced angiogenesis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/a172aad4b1524006b50e6401ef327d22
work_keys_str_mv	AT jihyejang clec14ahsp701ainteractionregulateshsp701ainducedangiogenesis AT mirakim clec14ahsp701ainteractionregulateshsp701ainducedangiogenesis AT taekkeunkim clec14ahsp701ainteractionregulateshsp701ainducedangiogenesis AT wooranlee clec14ahsp701ainteractionregulateshsp701ainducedangiogenesis AT jongheonkim clec14ahsp701ainteractionregulateshsp701ainducedangiogenesis AT kyunheo clec14ahsp701ainteractionregulateshsp701ainducedangiogenesis AT sukmooklee clec14ahsp701ainteractionregulateshsp701ainducedangiogenesis
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CLEC14a-HSP70-1A interaction regulates HSP70-1A-induced angiogenesis

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