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

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...

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Autores principales: Jang, Jihye, Kim, Mi Ra, Kim, Taek-Keun, Lee, Woo Ran, Kim, Jong Heon, Heo, Kyun, Lee, Sukmook
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5587741/
https://www.ncbi.nlm.nih.gov/pubmed/28878328
http://dx.doi.org/10.1038/s41598-017-11118-y
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author Jang, Jihye
Kim, Mi Ra
Kim, Taek-Keun
Lee, Woo Ran
Kim, Jong Heon
Heo, Kyun
Lee, Sukmook
author_facet Jang, Jihye
Kim, Mi Ra
Kim, Taek-Keun
Lee, Woo Ran
Kim, Jong Heon
Heo, Kyun
Lee, Sukmook
author_sort Jang, Jihye
collection PubMed
description 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.
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spelling pubmed-55877412017-09-13 CLEC14a-HSP70-1A interaction regulates HSP70-1A-induced angiogenesis Jang, Jihye Kim, Mi Ra Kim, Taek-Keun Lee, Woo Ran Kim, Jong Heon Heo, Kyun Lee, Sukmook Sci Rep Article 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. Nature Publishing Group UK 2017-09-06 /pmc/articles/PMC5587741/ /pubmed/28878328 http://dx.doi.org/10.1038/s41598-017-11118-y Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Jang, Jihye
Kim, Mi Ra
Kim, Taek-Keun
Lee, Woo Ran
Kim, Jong Heon
Heo, Kyun
Lee, Sukmook
CLEC14a-HSP70-1A interaction regulates HSP70-1A-induced angiogenesis
title 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_short CLEC14a-HSP70-1A interaction regulates HSP70-1A-induced angiogenesis
title_sort clec14a-hsp70-1a interaction regulates hsp70-1a-induced angiogenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5587741/
https://www.ncbi.nlm.nih.gov/pubmed/28878328
http://dx.doi.org/10.1038/s41598-017-11118-y
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