HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 3, 1790-1796, January 21, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/3/1790    most recent M410775200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Liu, F. Articles by Gong, C.-X. Search for Related Content PubMed PubMed Citation Articles by Liu, F. Articles by Gong, C.-X. Social Bookmarking                      What's this?

Dephosphorylation of Tau by Protein Phosphatase 5

IMPAIRMENT IN ALZHEIMER'S DISEASE^*

Fei Liu, Khalid Iqbal, Inge Grundke-Iqbal, Sandra Rossie¶, and Cheng-Xin Gong||

From the New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York 10314 and ^¶Department of Biochemistry, Purdue University, West Lafayette, Indiana 47907

Protein phosphatase (PP) 5 is highly expressed in the mammalian brain, but few physiological substrates have yet been identified. Here, we investigated the kinetics of dephosphoryation of phospho-tau by PP5 and found that PP5 had a K_m of 8–13 µM toward tau, which is similar to that of PP2A, the major known tau phosphatase. This K_m value is within the range of intraneuronal tau concentration in human brain, suggesting that tau could be a physiological substrate of both PP5 and PP2A. PP5 dephosphorylated tau at all 12 Alzheimer's disease (AD)-associated abnormal phosphorylation sites studied, with different efficiency toward each site. Thr²⁰⁵, Thr²¹², and Ser⁴⁰⁹ of tau were the most favorable sites; Ser¹⁹⁹, Ser²⁰², Ser²¹⁴, Ser³⁹⁶, and Ser⁴⁰⁴ were less favorable sites; and Ser²⁶² was the poorest site for PP5. Overexpression of PP5 in PC12 cells resulted in dephosphorylation of tau at multiple phosphorylation sites. The activity but not the protein level of PP5 was found to be decreased by 20% in AD neocortex. These results suggest that tau is probably a physiological substrate of PP5 and that the abnormal hyperphosphorylation of tau in AD might result in part from the decreased PP5 activity in the diseased brains.

Received for publication, September 20, 2004 , and in revised form, November 8, 2004.

^* This work was supported by the New York State Office of Mental Retardation and Developmental Disabilities; Alzheimer Association Grant NIRG-03-4721 (to F. L.); National Institutes of Health Grants AG16760 (to C.-X. G.), AG19158 (to K. I.), and NS31221 (to S. R.); and an award from the Li Foundation, Inc. USA (to C.-X. G.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence may be addressed: Dept. of Neurochemistry, New York State Institute for Basic Research, 1050 Forest Hill Rd., Staten Island, NY 10314. Tel.: 718-494-5390; Fax: 718-494-1080; E-mail: feiliu63{at}hotmail.com. || To whom correspondence may be addressed: Dept. of Neurochemistry, New York State Institute for Basic Research, 1050 Forest Hill Rd., Staten Island, NY 10314. Tel.: 718-494-5248; Fax: 718-494-1080; E-mail: cxgong{at}ultinet.net.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. Gentile, T. Darden, C. Erxleben, C. Romeo, A. Russo, N. Martin, S. Rossie, and D. L. Armstrong Rac GTPase signaling through the PP5 protein phosphatase PNAS, March 28, 2006; 103(13): 5202 - 5206. [Abstract] [Full Text] [PDF]

				F. Liu, I. Grundke-Iqbal, K. Iqbal, Y. Oda, K. Tomizawa, and C.-X. Gong Truncation and Activation of Calcineurin A by Calpain I in Alzheimer Disease Brain J. Biol. Chem., November 11, 2005; 280(45): 37755 - 37762. [Abstract] [Full Text] [PDF]