Philippova, Maria and Ivanov, Danila and Joshi, Manjunath B. and Kyriakakis, Emmanouil and Rupp, Katharina and Afonyushkin, Taras and Bochkov, Valery and Erne, Paul and Resink, Therese J.. (2008) Identification of proteins associating with glycosylphosphatidylinositol- anchored T-cadherin on the surface of vascular endothelial cells: role for Grp78/BiP in T-cadherin-dependent cell survival. Molecular and Cellular Biology, 28 (12). pp. 4004-4017.
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Official URL: https://edoc.unibas.ch/63323/
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Abstract
There is scant knowledge regarding how cell surface lipid-anchored T-cadherin (T-cad) transmits signals through the plasma membrane to its intracellular targets. This study aimed to identify membrane proteins colocalizing with atypical glycosylphosphatidylinositol (GPI)-anchored T-cad on the surface of endothelial cells and to evaluate their role as signaling adaptors for T-cad. Application of coimmunoprecipitation from endothelial cells expressing c-myc-tagged T-cad and high-performance liquid chromatography revealed putative association of T-cad with the following proteins: glucose-related protein GRP78, GABA-A receptor alpha1 subunit, integrin beta3, and two hypothetical proteins, LOC124245 and FLJ32070. Association of Grp78 and integrin beta3 with T-cad on the cell surface was confirmed by surface biotinylation and reciprocal immunoprecipitation and by confocal microscopy. Use of anti-Grp78 blocking antibodies, Grp78 small interfering RNA, and coexpression of constitutively active Akt demonstrated an essential role for surface Grp78 in T-cad-dependent survival signal transduction via Akt in endothelial cells. The findings herein are relevant in the context of both the identification of transmembrane signaling partners for GPI-anchored T-cad as well as the demonstration of a novel mechanism whereby Grp78 can influence endothelial cell survival as a cell surface signaling receptor rather than an intracellular chaperone.
Faculties and Departments: | 03 Faculty of Medicine > Departement Biomedizin > Further Research Groups at DBM > Signal Transduction (Resink/Erne) |
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UniBasel Contributors: | Resink, Thérèse J. |
Item Type: | Article, refereed |
Article Subtype: | Research Article |
Publisher: | American Society for Microbiology |
ISSN: | 0270-7306 |
e-ISSN: | 1098-5549 |
Note: | Publication type according to Uni Basel Research Database: Journal article |
Related URLs: | |
Identification Number: |
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Last Modified: | 10 Aug 2020 16:23 |
Deposited On: | 10 Aug 2020 16:23 |
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