کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2803365 1156736 2006 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Novel actions of IGFBP-3 on intracellular signaling pathways of insulin-secreting cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی علوم غدد
پیش نمایش صفحه اول مقاله
Novel actions of IGFBP-3 on intracellular signaling pathways of insulin-secreting cells
چکیده انگلیسی

Understanding mechanisms underlying apoptotic destruction of insulin-secreting cells is critical to validate therapeutic targets for type 1 diabetes mellitus. We recently reported insulin-like growth factor binding protein-3 (IGFBP-3) as a novel mediator of apoptosis in insulin-secreting cells. In light of emerging IGF-independent roles for IGFBP-3, we investigated the mechanisms underlying actions of the novel, recombinant human mutant G56G80G81-IGFBP-3, which lacks intrinsic IGF binding affinity. Using the rat insulinoma RINm5F cell line, we report the first studies in insulin-secreting cells that IGFBP-3 selectively suppresses multiple, key intracellular phosphorelays. By immunoblot, we demonstrate that G56G80G81-IGFBP-3 suppresses phosphorylation of c-raf-MEK-ERK pathway and p38 kinase in time-dependent and dose-dependent manners. SAPK/JNK signaling was unaffected. These data delineate several novel intracellular sites of action for IGFBP-3 in insulin-secreting cells.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Growth Hormone & IGF Research - Volume 16, Issue 1, February 2006, Pages 41–48
نویسندگان
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