کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1924856 1536316 2015 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The C-terminal tail inhibitory phosphorylation sites of PTEN regulate its intrinsic catalytic activity and the kinetics of its binding to phosphatidylinositol-4,5-bisphosphate
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
The C-terminal tail inhibitory phosphorylation sites of PTEN regulate its intrinsic catalytic activity and the kinetics of its binding to phosphatidylinositol-4,5-bisphosphate
چکیده انگلیسی


• C-terminal tail phosphorylation inhibits the intrinsic catalytic activity of PTEN.
• Dephosphorylation of all four sites is required for full activation of PTEN.
• Phospholipid PI-4,5-P2 does not activate the intrinsic catalytic activity of PTEN.
• Dephosphorylation of all four sites reduces the PTEN affinity to PI-4,5-P2.

Dephosphorylation of four major C-terminal tail sites and occupancy of the phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2]-binding site of PTEN cooperate to activate its phospholipid phosphatase activity and facilitate its recruitment to plasma membrane. Our investigation of the mechanism by which phosphorylation of these C-terminal sites controls the PI(4,5)P2-binding affinity and catalytic activity of PTEN resulted in the following findings. First, dephosphorylation of all four sites leads to full activation; and phosphorylation of any one site significantly reduces the intrinsic catalytic activity of PTEN. These findings suggest that coordinated inhibition of the upstream protein kinases and activation of the protein phosphatases targeting the four sites are needed to fully activate PTEN phosphatase activity. Second, PI(4,5)P2 cannot activate the phosphopeptide phosphatase activity of PTEN, suggesting that PI(4,5)P2 can only activate the phospholipid phosphatase activity but not the phosphoprotein phosphatase activity of PTEN. Third, dephosphorylation of all four sites significantly decreases the affinity of PTEN for PI(4,5)P2. Since PI(4,5)P2 is a major phospholipid co-localizing with the phospholipid- and phosphoprotein-substrates in plasma membrane, we hypothesise that the reduced affinity facilitates PTEN to “hop” on the plasma membrane to dephosphorylate these substrates.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Archives of Biochemistry and Biophysics - Volume 587, 1 December 2015, Pages 48–60
نویسندگان
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