Phosphatase Activity Toward Abnormally Phosphorylated τ: Decrease in Alzheimer Disease Brain |
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Authors: | Cheng-Xin Gong Sadia Shaikh Jian-Zhi Wang Tanweer Zaidi Inge Grundke-Iqbal Khalid Iqbal |
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Affiliation: | New York State Institute for Basic Research in Development Disabilities, Staten Island, New York, U.S.A. |
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Abstract: | Abstract: Microtubule-associated protein τ is abnormally hyperphosphorylated and aggregated in affected neurons of Alzheimer disease brain. This hyperphosphorylated τ can be dephosphorylated at some of the abnormal phosphorylated sites by purified protein phosphatase-1, 2A, and 2B in vitro. In the present study, we have developed an assay to measure protein phosphatase activity toward τ-1 sites (Ser199/Ser202) using the hyperphosphorylated τ isolated from Alzheimer disease brain as substrate. Using this assay, we have identified that in normal brain, protein phosphatase-2A and 2B and, to a lesser extent, 1 are involved in the dephosphorylation of τ. The K m values of dephosphorylation of the hyperphosphorylated τ by protein phosphatase-2A and 2B are similar. The τ phosphatase activity is decreased by ∼30% in brain of Alzheimer disease patients compared with those of age-matched controls. These findings suggest that a defect of protein phosphatase could be the cause of the abnormal hyperphosphorylation of τ in Alzheimer disease. |
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Keywords: | Microtubule-associated protein τ Protein phosphatase Protein dephosphorylation Alzheimer disease |
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