New multiple hamartoma syndrome genetics study findings have been published by scientists at University of Melbourne, BioTechnology Institute
2007 JUL 31 -- Current study results from the report, "PTEN catalysis of phospholipid dephosphorylation reaction follows a two-step mechanism in which the conserved aspartate-92 does not function as the general acid--mechanistic analysis of a familial Cowden disease-associated PTEN mutation," have been published. According to recent research published in the journal Cellular Signalling, "PTEN exerts its tumor suppressor function by dephosphorylating the phospholipid second messenger phosphatidylinositol-3,4,5-trisphosphate (PIP(3)). Herein, we demonstrate that the PTEN-catalysed PIP(3) dephosphorylation reaction involves two-steps: (i) formation of a phosphoenzyme intermediate (PE) in which Cys-124 in the active site is thiophosphorylated, and (ii) hydrolysis of PE." "For protein tyrosine-and dual-specificity phosphatases, catalysis requires the participation of a conserved active site aspartate as the general acid in Step 1. Its mutation to alanine severely limits PE formation. However, mutation of the homologous Asp-92 in PTEN does not significantly limit PE formation, indicating that Asp-92 does not act as the general acid. G129E is a common germline PTEN mutations found in Cowden syndrome patients. Mechanistic analysis reveals that this mutation inactivates PTEN by both significantly slowing down Step 1 and abolishing the ability to catalyse Step 2," wrote Y. Xiao and colleagues, University of Melbourne, BioTechnology Institute. The researchers concluded: "Taken together, our results highlight the mechanistic similarities and differences between PTEN and the conventional protein phosphatases and reveal how a disease-associated mutation inactivates PTEN." Xiao and colleagues published their study in Cellular Signalling (PTEN catalysis of phospholipid dephosphorylation reaction follows a two-step mechanism in which the conserved aspartate-92 does not function as the general acid--mechanistic analysis of a familial Cowden disease-associated PTEN mutation. Cellular Signalling, 2007;19(7):1434-45). For additional information, contact Y. Xiao, University of Melbourne, Dept. of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, Parkville, Victoria 3010, Australia. The publisher's contact information for the journal Cellular Signalling is: Elsevier Science Inc., 360 Park Avenue South, New York, NY 10010-1710, USA. Keywords: Australia, Parkville, Multiple Hamartoma Syndrome Genetics, Cellular, Multiple Hamartoma Syndrome. This article was prepared by Life Science Weekly editors from staff and other reports. Copyright 2007, Life Science Weekly via NewsRx.com.
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