Regulation of protein phosphatase 2A catalytic activity by alpha4 protein and its yeast homolog Tap42.
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.
Nanahoshi
M
M
Biosignal Research Center, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe, 657-8501, Japan.
Nishiuma
T
T
Tsujishita
Y
Y
Hara
K
K
Inui
S
S
Sakaguchi
N
N
Yonezawa
K
K
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002384:Catalysis; D002460:Cell Line; D039561:Eukaryotic Initiation Factor-4E; D005656:Fungal Proteins / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007700:Kinetics; D008322:Mammals; D018832:Molecular Chaperones; D010448:Peptide Initiation Factors / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D054648:Protein Phosphatase 2; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction; D013379:Substrate Specificity; D014162:Transfection
D048868:Adaptor Proteins, Signal Transducing; D039561:Eukaryotic Initiation Factor-4E; D005656:Fungal Proteins; C490467:IGBP1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; D010448:Peptide Initiation Factors; D010750:Phosphoproteins; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; C100984:TAP42 protein, S cerevisiae; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2