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Journal of Virology, September 1999, p. 7390-7398, Vol. 73, No. 9
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Catalytically Inactive Protein Phosphatase 2A Can Bind to Polyomavirus Middle Tumor Antigen and Support Complex Formation with pp60c-src

Egon Ogris,1,2 Ingrid Mudrak,2 Elsa Mak,1,dagger Daryl Gibson,1 and David C. Pallas1,3,*

Division of Cellular and Molecular Biology, Dana-Farber Cancer Institute, and Department of Pathology, Harvard Medical School, Boston, Massachusetts 021151; Institute of Molecular Biology, University of Vienna, A-1030 Vienna, Austria2; and Department of Biochemistry and Winship Cancer Center, Emory University School of Medicine, Atlanta, Georgia 303223

Received 19 March 1999/Accepted 2 June 1999

Interaction between the heterodimeric form of protein phosphatase 2A (PP2A) and polyomavirus middle T antigen (MT) is required for the subsequent assembly of a transformation-competent MT complex. To investigate the role of PP2A catalytic activity in MT complex formation, we undertook a mutational analysis of the PP2A 36-kDa catalytic C subunit. Several residues likely to be involved in the dephosphorylation mechanism were identified and mutated. The resultant catalytically inactive C subunit mutants were then analyzed for their ability to associate with a cellular (B subunit) or a viral (MT) B-type subunit. Strikingly, while all of the inactive mutants were severely impaired in their interaction with B subunit, most of these mutants formed complexes with polyomavirus MT. These findings indicate a potential role for these catalytically important residues in complex formation with cellular B subunit, but not in complex formation with MT. Transformation-competent MT is known to associate with, and modulate the activity of, several cellular proteins, including pp60c-src family kinases. To determine whether association of MT with an active PP2A A-C heterodimer is necessary for subsequent association with pp60c-src, catalytically inactive C subunits were examined for their ability to form complexes containing pp60c-src in MT-expressing cells. Two catalytically inactive C subunit mutants that efficiently formed complexes with MT also formed complexes that included an active pp60c-src kinase, demonstrating that PP2A activity is not essential in cis in MT complexes for subsequent pp60c-src association.

* Corresponding author. Mailing address: Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Rd., Atlanta, GA 30322. Phone: (404) 727-5620. Fax: (404) 727-3231. E-mail: dpallas{at}emory.edu.

dagger Present address: Cubist Pharmaceuticals, Inc., Cambridge, MA 02139.

Journal of Virology, September 1999, p. 7390-7398, Vol. 73, No. 9
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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