کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8322661 | 1539880 | 2015 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Threonine 34 phosphorylation by phosphoinositide-dependent protein kinase 1 facilitates dissociation of Akt from the plasma membrane
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کلمات کلیدی
mTORC2PKCζPIK3Mitogen-activated protein kinase-activated protein kinase 2Protein kinase C zetaPDKPIP3MAPKAPK2PDK1IGFAkt - آکتMembrane translocation - انتقال محفظهSurface plasmon resonance - تشدید پلاسمون سطحیSPR - تشدید پلاسمون سطحیRegulatory domain - دامنه نظارتیkinase domain - دامنه کینازMass spectrometry - طیف سنجی جرمیInsulin-like growth factor - فاکتور رشد مانند انسولینPhosphatidylserine - فسفاتیدیلسرینphosphatidylinositol 3,4,5-trisphosphate - فسفاتیدیلینواستیل 3،4،5-تری فسفاتAkt activation - فعال سازی فعالMammalian target of rapamycin complex 2 - هدف پستانداران رپامایسین 2Pleckstrin Homology - همخوانی Pleckstrinprotein kinase B - پروتئین کیناز B
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
Akt is a key mediator of cell proliferation, survival and metabolism. After translocation to the membrane and phosphorylation at T308 and S473, the activated Akt dissociates from the plasma membrane to cytoplasm, which is an important step to phosphorylate its downstream targets. In addition to its central role in regulating the kinase activity, phosphorylation of T308 in the kinase loop has been reported to be necessary for this dissociation process. However, it is not clear whether the membrane detachment requires further mechanisms. In the present report, we demonstrate that membrane dissociation of Akt requires phosphoinositide-dependent protein kinase 1 (PDK1) which directly phosphorylates not only T308 but also T34 in the pleckstrin homology (PH) domain. Like T308, T34 was phosphorylated in a phosphatidylinositol 3,4,5-trisphosphate- and phosphatidylserine-dependent manner. Phosphorylation of T34 also occurred in cells following growth factor stimulation, concurrently with T308 phosphorylation. Moreover, when T34 was mutated to aspartic acid (T34D) to mimic its phosphorylation, Akt-membrane association assessed by surface plasmon resonance spectroscopy was significantly reduced. In cells, this mutation impaired the IGF-induced Akt membrane translocation and subsequent phosphorylation at T308 and S473. Taken together, our results demonstrate that T34 phosphorylation by PDK1 promotes the membrane dissociation of activated Akt for its downstream action through attenuating membrane binding affinity. This membrane dissociation mechanism offers a new insight for Akt activation process and provides a potential new target for controlling the Akt-dependent cellular processes.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The International Journal of Biochemistry & Cell Biology - Volume 64, July 2015, Pages 195-201
Journal: The International Journal of Biochemistry & Cell Biology - Volume 64, July 2015, Pages 195-201
نویسندگان
Bill X. Huang, Rachel Lee, Mohammed Akbar, Hee-Yong Kim,