کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5505920 | 1400282 | 2017 | 29 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
ADP-ribosylation factor-like GTPase 15 enhances insulin-induced AKT phosphorylation in the IR/IRS1/AKT pathway by interacting with ASAP2 and regulating PDPK1 activity
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کلمات کلیدی
PIP3PDPK1PIP5KPIP2GEFARFAkt - آکتGAP - شکافADP-ribosylation factor - فاکتور ADP-ribosylationguanine nucleotide-exchange factor - فاکتور تبادل نوکئوتید گوانینphosphatidylinositol-4,5-bisphosphate - فسفاتیدیلینستول-4،5-بیسفسفاتphosphatidylinositol-3,4,5-trisphosphate - فسفاتیدیلینواستیل 3،4،5-تری فسفاتphosphatidylinositol-4-phosphate 5-kinase - فسفاتیدیلینواستیل 4-فسفات 5-کینازPhosphorylation - فسفریلاسیونInsulin resistance - مقاومت به انسولینGTPase-activating protein - پروتئین فعال GTPase3-phosphoinositide-dependent protein kinase 1 - پروتئین کیناز 1 وابسته به 3-فسفوئوزیتید
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Decreased phosphorylation in the insulin signalling pathway is a hallmark of insulin resistance. The causes of this phenomenon are complicated and multifactorial. Recently, genomic analyses have identified ARL15 as a new candidate gene related to diabetes. However, the ARL15 protein function remains unclear. Here, we show that ARL15 is upregulated by insulin stimulation. This effect was impaired in insulin-resistant pathophysiology in TNF-α-treated C2C12 myotubes and in the skeletal muscles of leptin knockout mice. In addition, ARL15 localized to the cytoplasm in the resting state and accumulated in the Golgi apparatus around the nucleus upon insulin stimulation. ARL15 overexpression can enhance the phosphorylation of the key insulin signalling pathway molecules IR, IRS1 and AKT in C2C12 myotubes. Moreover, ARL15 knockdown can also specifically inhibit the phosphorylation of PDPK1 Ser241, thereby reducing PDPK1 activity and its downstream phosphorylation of AKT Thr308. Co-immunoprecipitation assays identified ASAP2 as an ARL15-interacting protein. In conclusion, we have identified that ARL15 acts as an insulin-sensitizing effector molecule to upregulate the phosphorylation of members of the canonical IR/IRS1/PDPK1/AKT insulin pathway by interacting with its GAP ASAP2 and activating PDPK1. This research may provide new insights into GTPase-mediated insulin signalling regulation and facilitate the development of new pharmacotherapeutic targets for insulin sensitization.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 486, Issue 4, 13 May 2017, Pages 865-871
Journal: Biochemical and Biophysical Research Communications - Volume 486, Issue 4, 13 May 2017, Pages 865-871
نویسندگان
Jie Zhao, Min Wang, Wuquan Deng, Daping Zhong, Youzhao Jiang, Yong Liao, Bing Chen, Xiaoli Zhang,