|
 |
|
|
| Subject Categories: Signal Transduction | Genome Stability & Dynamics |
|
| The EMBO Journal
(2004) 23, 4451–4461, doi:10.1038/sj.emboj.7600455 Published online 28 October 2004 |
|
| Autophosphorylation of ataxia-telangiectasia mutated is regulated by protein phosphatase 2A |
|
|
| Aaron A Goodarzi1, 2, 4, Jyoti C Jonnalagadda3, 4, Pauline Douglas2, David Young3, Ruiqiong Ye2, Greg B G Moorhead1, Susan P Lees-Miller1, 2 and Kum Kum Khanna3 |
|
|
1 Department of Biological Sciences, University of Calgary, Calgary, AB, Canada 2 Department of Biochemistry & Molecular Biology, University of Calgary, Calgary, AB, Canada 3 Queensland Institute of Medical Research, Brisbane, Australia To whom correspondence should be addressed Susan P Lees-Miller, Department of Biochemistry & Molecular Biology, University of Calgary, 3330 Hospital Drive, NW, Calgary, AB, Canada T2N 4N1. Tel.: +1 403 220 7628; Fax: +1 403 210 3899; E-mail: leesmill@ucalgary.ca Kum Kum Khanna, Queensland Institute of Medical Research, 300 Herston Road, Herston, QLD 4029, Australia. Tel.: +61 7 33620338; Fax: +61 7 33620105; E-mail: kumkumK@qimr.edu.au 4 These two authors contributed equally to this work Received 22 July 2004; Accepted 1 October 2004; Published online 28 October 2004. |
|
|
|
| Abstract |
|
Ionizing radiation induces autophosphorylation of the ataxia-telangiectasia mutated (ATM) protein kinase on serine 1981; however, the precise mechanisms that regulate ATM activation are not fully understood. Here, we show that the protein phosphatase inhibitor okadaic acid (OA) induces autophosphorylation of ATM on serine 1981 in unirradiated cells at concentrations that inhibit protein phosphatase 2A-like activity in vitro. OA did not induce  -H2AX foci, suggesting that it induces ATM autophosphorylation by inactivation of a protein phosphatase rather than by inducing DNA double-strand breaks. In support of this, we show that ATM interacts with the scaffolding (A) subunit of protein phosphatase 2A (PP2A), that the scaffolding and catalytic (C) subunits of PP2A interact with ATM in undamaged cells and that immunoprecipitates of ATM from undamaged cells contain PP2A-like protein phosphatase activity. Moreover, we show that IR induces phosphorylation-dependent dissociation of PP2A from ATM and loss of the associated protein phosphatase activity. We propose that PP2A plays an important role in the regulation of ATM autophosphorylation and activity in vivo. |
|
| Keywords: ATM, autophosphorylation, okadaic acid, protein phosphatase |
|
|
|
Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated NEWS AND VIEWSCheckpoint signalling: focusing on 53BP1 Nature Cell Biology News and Views (01 Dec 2002) Tudor domains track down DNA breaks Nature Cell Biology News and Views (01 Dec 2004) RESEARCHA GTP-binding adapter protein couples TRAIL receptors to apoptosis-inducing proteins Nature Immunology Article (01 Jun 2001) Circumventing tolerance to a human MDM2-derived tumor antigen by TCR gene transfer Nature Immunology Article (01 Oct 2001) |
|
|
| |
| |
| |
 | Email link to a friend |
| |
 | Download PDF |
| |
 | Full text |
| |
| |
| |
 | Next article |
| |
 | Previous article |
| |
 | Table of contents |
| |
| |
 | Rights and permissions |
| |
 | Reprints |
| |
| |
| |
 Register for table of contents by email | |
| |
| |
| |
