کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5509342 | 1538511 | 2017 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Enzymatic cleavage of myoferlin releases a dual C2-domain module linked to ERK signalling
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کلمات کلیدی
MyoferlinOTOFERKCAPN1Calpain-2Calpain-1SLPsDOCsCAPNS1OtoferlinPhosphorylated ERK - ERK فسفریلیت شدهMAPK - MAPKKnock-down - دست کشیدنDysferlin - دیسفرلینBreast cancer - سرطان پستانCell signalling - سیگنالینگ سلولknockout - ناکاوتProteolysis - پروتئولیزmitogen-activated protein kinase - پروتئین کیناز فعال با mitogenPERK - پرکCalpain - کالپینextracellular-signal-regulated kinase - کیناز تنظیم شده خارج سلولی سیگنال
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
Myoferlin and dysferlin are closely related members of the ferlin family of Ca2Â +-regulated vesicle fusion proteins. Dysferlin is proposed to play a role in Ca2Â +-triggered vesicle fusion during membrane repair. Myoferlin regulates endocytosis, recycling of growth factor receptors and adhesion proteins, and is linked to the metastatic potential of cancer cells. Our previous studies establish that dysferlin is cleaved by calpains during membrane injury, with the cleavage motif encoded by alternately-spliced exon 40a. Herein we describe the cleavage of myoferlin, yielding a membrane-associated dual C2 domain 'mini-myoferlin'. Myoferlin bears two enzymatic cleavage sites: a canonical cleavage site encoded by exon 38 within the C2DE domain; and a second cleavage site in the linker adjacent to C2DE, encoded by alternately-spliced exon 38a, homologous to dysferlin exon 40a. Both myoferlin cleavage sites, when introduced into dysferlin, can functionally substitute for exon 40a to confer Ca2Â +-triggered calpain cleavage in response to membrane injury. However, enzymatic cleavage of myoferlin is complex, showing both constitutive or Ca2Â +-enhanced cleavage in different cell lines, that is not solely dependent on calpains-1 or -2. The functional impact of myoferlin cleavage was explored through signalling protein phospho-protein arrays revealing specific activation of ERK1/2 by ectopic expression of cleavable myoferlin, but not an uncleavable isoform. In summary, we molecularly define two enzymatic cleavage sites within myoferlin and demonstrate 'mini-myoferlin' can be detected in human breast cancer tumour samples and cell lines. These data further illustrate that enzymatic cleavage of ferlins is an evolutionarily preserved mechanism to release functionally specialized mini-modules.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 33, May 2017, Pages 30-40
Journal: Cellular Signalling - Volume 33, May 2017, Pages 30-40
نویسندگان
Ann-Katrin Piper, Samuel E. Ross, Gregory M. Redpath, Frances A. Lemckert, Natalie Woolger, Adam Bournazos, Peter A. Greer, Roger B. Sutton, Sandra T. Cooper,