کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1951241 1055751 2008 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Modulation by insulin-like growth factor I of the phosphatase PTEN in astrocytes
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Modulation by insulin-like growth factor I of the phosphatase PTEN in astrocytes
چکیده انگلیسی

Characterization of intracellular pathways underlying the pleiotropic actions of insulin-like growth factor-I (IGF-I) on brain cells is incomplete. We analyzed IGF-I signalling on astrocytes through the canonical phosphatidylinositol 3-kinase (PI3K)/Akt pathway and focused on possible changes in PTEN, a phosphatase that modulates IGF-I signalling by inhibiting Akt activation and, in turn is positively regulated by PI3K. After exposure of astrocytes to IGF-I, PTEN mRNA and protein levels were reduced and its phosphatase activity diminished. Inhibition of PTEN involved activation of a PI3K/protein kinase C (PKC) pathway that decreased in a proteasome-dependent step the levels of the transcription factor Egr-1, a key regulator of PTEN levels in astrocytes, causing decreased binding of Egr-1 to the PTEN promoter. Enhanced mitogenesis in PTEN siRNA-transduced astrocytes after IGF-I suggested that reduced PTEN may be a permissive factor for the mitogenic activity of IGF-I. Subsequent recovery of reduced PTEN required also activation by IGF-I of PI3K to recruit in this case protein kinase A (PKA) which stimulated Egr-1 levels and, consequently PTEN synthesis. Because basal levels of PTEN in astrocytes are also governed by PI3K, IGF-I appears to modulate PTEN in astrocytes by redirecting its homeostasic control through PI3K in a timed fashion.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research - Volume 1783, Issue 5, May 2008, Pages 803–812
نویسندگان
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