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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| Format: | Article |
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Nature Portfolio
2017-09-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-11118-y |
| _version_ | 1818994252983566336 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-20T20:55:00Z |
| format | Article |
| id | doaj.art-a172aad4b1524006b50e6401ef327d22 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-20T20:55:00Z |
| publishDate | 2017-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-a172aad4b1524006b50e6401ef327d222022-12-21T19:26:51ZengNature PortfolioScientific Reports2045-23222017-09-017111210.1038/s41598-017-11118-yCLEC14a-HSP70-1A interaction regulates HSP70-1A-induced angiogenesisJihye Jang0Mi Ra Kim1Taek-Keun Kim2Woo Ran Lee3Jong Heon Kim4Kyun Heo5Sukmook Lee6Research Center, Scripps Korea Antibody InstituteResearch Center, Scripps Korea Antibody InstituteResearch Center, Scripps Korea Antibody InstituteResearch Center, Scripps Korea Antibody InstituteDepartment of System Cancer Science, Graduate School of Cancer Science and Policy, National Cancer CenterNew Experimental Therapeutics Branch, Research Institute, National Cancer CenterResearch Center, Scripps Korea Antibody InstituteAbstract 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.https://doi.org/10.1038/s41598-017-11118-y |
| spellingShingle | 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 Scientific Reports |
| 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 |
| url | https://doi.org/10.1038/s41598-017-11118-y |
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