کد مقاله کد نشریه سال انتشار مقاله انگلیسی ترجمه فارسی نسخه تمام متن
5505043 1400259 2017 7 صفحه PDF سفارش دهید دانلود رایگان
عنوان انگلیسی مقاله ISI
Functional characterization of lysophosphatidic acid receptor 1 mutants identified in rat cancer tissues
ترجمه فارسی عنوان
مشخصه عملکردی جهش های گیرنده 1 اسید فسفاتیدیک در سلول های سرطانی موش صحرایی
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موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
چکیده انگلیسی
Lysophosphatidic acid (LPA), an extracellular lipid mediator, exerts various cellular effects through activation of LPA receptors, LPA1-LPA6, in many types of cells including cancer cells. We recently found several missense mutations of Lpar1 in rat cancer tissues. One of these mutations is located at the extracellular tip of the seventh transmembrane domain of LPA1, and another three mutations are found within the NPXXY motif in the seventh transmembrane domain. These mutants are designated F295S LPA1 and P308S, I310T, and Y311H LPA1, respectively. Here, we examined the functions of these LPA1 mutants. Compared with wild-type (WT) LPA1, F295S, P308S, and I310T LPA1 showed decreased maximal responses in inhibition of cAMP formation, Ca2+ mobilization, and cytoskeletal changes. Y311H LPA1 failed to show LPA-induced cellular responses. However, these LPA1 mutants were internalized in response to LPA exposure. Finally, while WT and F295S LPA1 showed a similar, broad distribution throughout the cell, P308S, I310T, and Y311H LPA1 displayed a restricted cellular distribution and co-localized with the endoplasmic reticulum. These data suggest that the LPA1 mutants perturb LPA signaling in cancer tissues.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 486, Issue 3, 6 May 2017, Pages 767-773
نویسندگان
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