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Molecular and Cellular Biology, December 1998, p. 7556-7564, Vol. 18, No. 12
Department of Biochemistry, Tufts University
School of Medicine, Boston, Massachusetts
Received 3 June 1998/Returned for modification 9 July 1998/Accepted 10 September 1998
Polyomavirus causes a broad spectrum of tumors as the result of the
action of its early proteins. This work compares signaling from middle
T antigen (MT), the major transforming protein, to that from small T
antigen (ST). The abilities of MT mutants to promote cell cycle
progression in serum-starved NIH 3T3 cells were compared.
Transformation-defective mutants lacking association with SHC or with
phosphatidylinositol 3-kinase (PI3-K) retained the ability to induce
DNA synthesis as measured by bromodeoxyuridine incorporation. Only when
both interactions were lost in the Y250F/Y315F double mutant was MT
inactive. ST promoted cell cycle progression in a manner dependent on
its binding of protein phosphatase 2A (PP2A). Since the Y250F/Y315F MT
mutant was wild type for PP2A binding yet unable to promote cell cycle
progression, while ST was capable of promoting cell cycle progression,
these experiments revealed a functional difference in MT and ST
signaling via PP2A. Assays testing the abilities of MT and ST to induce
the c-fos promoter and to activate c-jun kinase led to the
same conclusion. ST, but not Y250F/Y315F MT, was able to activate the
c-fos promoter through its interaction with PP2A. In
contrast, MT, but not ST, was able to activate c-jun kinase by virtue
of its interaction with PP2A.
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Signaling from Polyomavirus Middle T and Small T
Defines Different Roles for Protein Phosphatase 2A
*
Corresponding author. Mailing address: Department of
Biochemistry, Tufts University School of Medicine, 136 Harrison Ave., Boston, MA 02111. Phone: (617) 636-6876. Fax: (617) 636-2409. E-mail:
bschaffh_pol{at}opal.tufts.edu.
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