کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10904029 | 1086553 | 2014 | 15 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Furin processing dictates ectodomain shedding of human FAT1 cadherin
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کلمات کلیدی
TGNPCCDNegative regulatory regionLDL-receptor related proteinHeterodimerisationICNLNRNRRECDLRPmAbMonoclonal antibody - آنتی بادی مونوکلونالextracellular domain - دامنه خارج سلولیintracellular domain - دامنه درون سلولیICD - دفیبریلاتورهای کاردیوورتر کاشتنیEctodomain shedding - ریزش اکتودومینTrans-Golgi network - شبکه Trans-GoljiFurin - فورینproprotein convertase - پروپروتئین تبدیل کننده
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Furin processing dictates ectodomain shedding of human FAT1 cadherin Furin processing dictates ectodomain shedding of human FAT1 cadherin](/preview/png/10904029.png)
چکیده انگلیسی
Fat1 is a single pass transmembrane protein and the largest member of the cadherin superfamily. Mouse knockout models and in vitro studies have suggested that Fat1 influences cell polarity and motility. Fat1 is also an upstream regulator of the Hippo pathway, at least in lower vertebrates, and hence may play a role in growth control. In previous work we have established that FAT1 cadherin is initially cleaved by proprotein convertases to form a noncovalently linked heterodimer prior to expression on the cell surface. Such processing was not a requirement for cell surface expression, since melanoma cells expressed both unprocessed FAT1 and the heterodimer on the cell surface. Here we further establish that the site 1 (S1) cleavage step to promote FAT1 heterodimerisation is catalysed by furin and we identify the cleavage site utilised. For a number of other transmembrane receptors that undergo heterodimerisation the S1 processing step is thought to occur constitutively but the functional significance of heterodimerisation has been controversial. It has also been generally unclear as to the significance of receptor heterodimerisation with respect to subsequent post-translational proteolysis that often occurs in transmembrane proteins. Exploiting the partial deficiency of FAT1 processing in melanoma cells together with furin-deficient LoVo cells, we manipulated furin expression to demonstrate that only the heterodimer form of FAT1 is subject to cleavage and subsequent release of the extracellular domain. This work establishes S1-processing as a clear functional prerequisite for ectodomain shedding of FAT1 with general implications for the shedding of other transmembrane receptors.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Cell Research - Volume 323, Issue 1, 15 April 2014, Pages 41-55
Journal: Experimental Cell Research - Volume 323, Issue 1, 15 April 2014, Pages 41-55
نویسندگان
Elham Sadeqzadeh, Charles E. de Bock, Natalie Wojtalewicz, Janet E. Holt, Nathan D. Smith, Matthew D. Dun, Irmgard Schwarte-Waldhoff, Rick F. Thorne,