کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10815228 | 1058461 | 2016 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
ERK5 induces ankrd1 for catecholamine biosynthesis and homeostasis in adrenal medullary cells
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کلمات کلیدی
ternary complex factorsPC12Extracellular-signal regulated kinase (ERK)NLSTBSTEGFNGFECLANKRD1TCFNuclear localizing signalSCGERKankyrin repeat domain 1RT-PCRHRPGAPDHbFGFnESDMEMDulbecco's modified Eagle's medium - Medal of Eagle اصلاح شده DulbeccoTris-buffered saline containing 0.1% Tween-20 - Tris-buffered saline حاوی 0.1٪ Tween-20 استenhanced chemiluminescence - بهبود شیمیایی لومنtyrosine hydroxylase - تیروزین هیدروکسیلازpheochromocytoma cells - سلولهای فئوکروموسیتوماnuclear export signal - سیگنال صادرات هسته ایepidermal growth factor - عامل رشد اپیدرمیPheochromocytoma - فئوکروموسیتومnerve growth factor - فاکتور رشد عصبNerve growth factor (NGF) - فاکتور رشد عصبی (NGF)fibroblast growth factor - فاکتور رشد فیبروبلاستSympathetic neurons - نورونهای سمپاتیکTyrosine hydroxylase (TH) - هیدروکسیلاز تیروزین (TH)reverse transcription-polymerase chain reaction - واکنش زنجیره ای رونویسی-پلیمراز معکوسHorseradish peroxidase - پراکسیداز هوررادیشextracellular signal-regulated kinase - کیناز تنظیم شده سیگنال خارج سلولیSuperior cervical ganglia - گانگلیس سرویکس برترglyceraldehyde-3-phosphate dehydrogenase - گلیسرالیدید-3-فسفات دهیدروژناز
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Extracellular signal-regulated kinases (ERKs) play important roles in proliferation, differentiation and gene expression. In our previous study, we demonstrated that both ERK5 and ERK1/2 were responsible for neurite outgrowth and tyrosine hydroxylase (TH) expression in rat pheochromocytoma cells (PC12) (J Biol Chem 284, 23,564-23,573, 2009). However, the functional differences between ERK5 and ERK1/2 signaling in neural differentiation remain unclear. In the present study, we show that ERK5, but not ERK1/2 regulates TH levels in rat sympathetic neurons. Furthermore, microarray analysis performed in PC12 cells using ERK5 and ERK1/2-specific inhibitors, identified ankyrin repeat domain 1 (ankrd1) as an ERK5-dependent and ERK1/2-independent gene. Here, we report a novel role of the ERK5/ankrd1 signaling in regulating TH levels and catecholamine biosynthesis. Ankrd1 mRNA was induced by nerve growth factor in time- and concentration-dependent manners. TH levels were reduced by ankrd1 knockdown with no changes in the mRNA levels, suggesting that ankrd1 was involved in stabilization of TH protein. Interestingly, ubiquitination of TH was enhanced and catecholamine biosynthesis was reduced by ankrd1 knockdown. Finally, we examined the relationship of ERK5 to TH levels in human adrenal pheochromocytomas. Whereas TH levels were correlated with ERK5 levels in normal adrenal medullas, ERK5 was down-regulated and TH was up-regulated in pheochromocytomas, indicating that TH levels are regulated by alternative mechanisms in tumors. Taken together, ERK5 signaling is required for catecholamine biosynthesis during neural differentiation, in part to induce ankrd1, and to maintain appropriate TH levels. This pathway is disrupted in pathological conditions.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 28, Issue 3, March 2016, Pages 177-189
Journal: Cellular Signalling - Volume 28, Issue 3, March 2016, Pages 177-189
نویسندگان
Yutaro Obara, Ryusuke Nagasawa, Wataru Nemoto, Michael J. Pellegrino, Maho Takahashi, Beth A. Habecker, Philip J.S. Stork, Osamu Ichiyanagi, Hiromi Ito, Yoshihiko Tomita, Kuniaki Ishii, Norimichi Nakahata,