Recent studies have revealed that the alpha4 protein, a mammalian homolog of yeast Tap42, is associated with the protein phosphatase 2A catalytic subunit (PP2A-C), however, effects of the association of alpha4 with PP2A-C on its phosphatase activity have not been examined, especially using physiologically relevant substrates in the signaling pathway of mTOR (the mammalian target of rapamycin) protein. Here, we report how this association affects the enzymatic activity of PP2A-C using the recombinant eIF-4E binding protein (4E-BP1) phosphorylated by immunoprecipitated mTOR as a substrate. PP2A-C dephosphorylated 4E-BP1 in vitro. The association of alpha4 and Tap42 with PP2A-C inhibited the phosphatase activity toward 4E-BP1. Rapamycin treatment, however, neither induced restoration of the phosphatase activity of PP2A-C nor caused dissociation of alpha4 and Tap42 from PP2A-C. Our study is the first report to reveal a potential regulatory role of alpha4 and Tap42 to inibit the phosphatase activity of PP2A-C toward the physiologically relevant substrate in the mTOR signaling: (C) 1998 Academic Press.
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Mt Sinai Hlth Syst, St Lukes Roosevelt Hosp Ctr, New York, NY USA
Mt Sinai Hlth Syst, Roosevelt Hosp, New York, NY USAMt Sinai Hlth Syst, St Lukes Roosevelt Hosp Ctr, New York, NY USA
Geraghty, P.
Eden, E.
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Mt Sinai Hlth Syst, Roosevelt Hosp, New York, NY USAMt Sinai Hlth Syst, St Lukes Roosevelt Hosp Ctr, New York, NY USA
Eden, E.
Pillai, M. V.
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Mt Sinai Hlth Syst, Roosevelt Hosp, New York, NY USAMt Sinai Hlth Syst, St Lukes Roosevelt Hosp Ctr, New York, NY USA
Pillai, M. V.
Campos, M. A.
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Univ Miami, Miller Sch Med, Miami, FL 33136 USAMt Sinai Hlth Syst, St Lukes Roosevelt Hosp Ctr, New York, NY USA
Campos, M. A.
McElvaney, N. G.
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Royal Coll Surgeons Ireland, Dublin, IrelandMt Sinai Hlth Syst, St Lukes Roosevelt Hosp Ctr, New York, NY USA
McElvaney, N. G.
Foronjy, R.
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New York Mt Sinai Hlth Syst, St Lukes Roosevelt Hosp Ctr, Div Pulm Crit Care & Sleep Med, New York, NY USAMt Sinai Hlth Syst, St Lukes Roosevelt Hosp Ctr, New York, NY USA