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• W1821233243 endingPage "1113" @default.
• W1821233243 startingPage "1101" @default.
• W1821233243 abstract "ABSTRACT β3 integrin adhesion molecules play important roles in wound repair and the regulation of vascular development and three β3 integrin isoforms (β3-A, -B, -C) have been described so far. Surface expression of β3 integrins is dynamically regulated through internalization of β3 integrins, however, the molecular mechanisms are understood incompletely. To evaluate the role of the cytoplasmic domain of β3 integrins for internalization, we have generated single chain chimeras with variant and mutated forms of β3 cytoplasmic domains. Upon transient transfection into chinese hamster ovary cells, it was found that the β3-A chimera had strongly reduced cell surface expression compared with the corresponding β3-B, or β3-C fusion proteins, or the tail-less constructs, whereas steady state levels of all chimeras were near identical. Studies employing cytoplasmic domain mutants showed that the NITY motif at β3-A 756-759 is critical for plasma membrane expression of β3-A. Furthermore, delivery of β3-A to the cell surface was specifically modulated by the cytoplasmic protein β3-endonexin, a previously described intracellular protein. Coexpression of the native, long form of β3-endonexin, which does not interact with the β3 tail, acted as a dominant negative inhibitor of β3-A-internalization and enhanced steady-state surface expression of the β3-A-chimera. Furthermore, anti-β3 antibody-induced internalization of the native β3 integrin (αIIbβ3) was dramatically reduced for the Tyr759-Ala substitution mutant αIIbβ3 (Y759A) and expression of the long isoform of β3-endonexin substantially decreased the internalization of wild-type αIIbβ3. Thus, the NITY motif of the beta-chain cytoplasmic domain is involved in stimulated internalization of the β3 integrin A isoform and β3-endonexin appears to couple the β3-A isoform to a specific receptor-recycling pathway." @default.
• W1821233243 created "2016-06-24" @default.
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• W1821233243 date "2001-03-15" @default.
• W1821233243 modified "2023-09-23" @default.
• W1821233243 title "The NITY motif of the beta-chain cytoplasmic domain is involved in stimulated internalization of the β3 integrin A isoform" @default.
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• W1821233243 doi "https://doi.org/10.1242/jcs.114.6.1101" @default.
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