Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/97309
Type: Artigo de periódico
Title: Identification And Characterization Of An Alternatively Spliced Isoform Of The Human Protein Phosphatase 2aα Catalytic Subunit
Author: Migueleti D.L.S.
Smetana J.H.C.
Nunes H.F.
Kobarg J.
Zanchin N.I.T.
Abstract: PP2A is the main serine/threonine-specific phosphatase in animal cells. The active phosphatase has been described as a holoenzyme consisting of a catalytic, a scaffolding, and a variable regulatory subunit, all encoded by multiple genes, allowing for the assembly of more than 70 different holoenzymes. The catalytic subunit can also interact with α4, TIPRL (TIP41, TOR signaling pathway regulator-like), the methyl-transferase LCMT-1, and the methyl-esterase PME-1. Here, we report that the gene encoding the catalytic subunit PP2Acα can generate two mRNA types, the standard mRNA and a shorter isoform, lacking exon 5, which we termed PP2Acα2. Higher levels of the PP2Acα2 mRNA, equivalent to the level of the longer PP2Acα mRNA, were detected in peripheral blood mononuclear cells that were left to rest for 24 h. After this time, the peripheral blood mononuclear cells are still viable and the PP2Acα2 mRNA decreases soon after they are transferred to culture medium, showing that generation of the shorter isoform depends on the incubation conditions. FLAG-tagged PP2Acα2 expressed in HEK293 is catalytically inactive. It displays a specific interaction profile with enhanced binding to the α4 regulatory subunit, but no binding to the scaffolding subunit and PME-1. Consistently, α4 out-competes PME-1 and LCMT-1 for binding to both PP2Acα isoforms in pulldown assays. Together with molecular modeling studies, this suggests that all three regulators share a common binding surface on the catalytic subunit. Our findings add important new insights into the complex mechanisms of PP2A regulation. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.
Editor: 
Rights: fechado
Identifier DOI: 10.1074/jbc.M111.283341
Address: http://www.scopus.com/inward/record.url?eid=2-s2.0-84856839156&partnerID=40&md5=6fff15197fe29fdfffc7ff77afb827a4
Date Issue: 2012
Appears in Collections:Unicamp - Artigos e Outros Documentos

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