Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/69110
Type: Artigo de periódico
Title: Identification and Characterization of an Alternatively Spliced Isoform of the Human Protein Phosphatase 2A alpha Catalytic Subunit
Author: Migueleti, DLS
Smetana, JHC
Nunes, HF
Kobarg, J
Zanchin, NIT
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 alpha 4, 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 PP2Ac alpha can generate two mRNA types, the standard mRNA and a shorter isoform, lacking exon 5, which we termed PP2Ac alpha 2. Higher levels of the PP2Ac alpha 2 mRNA, equivalent to the level of the longer PP2Ac alpha 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 PP2Ac alpha 2 mRNA decreases soon after they are transferred to culture medium, showing that generation of the shorter isoform depends on the incubation conditions. FLAG-tagged PP2Ac alpha 2 expressed in HEK293 is catalytically inactive. It displays a specific interaction profile with enhanced binding to the alpha 4 regulatory subunit, but no binding to the scaffolding subunit and PME-1. Consistently, alpha 4 out-competes PME-1 and LCMT-1 for binding to both PP2Ac alpha isoforms in pulldown assays. Together with molecular modeling studies, this suggests that all three regulators share a common binding surface on the catalytic sub-unit. Our findings add important new insights into the complex mechanisms of PP2A regulation.
Country: EUA
Editor: Amer Soc Biochemistry Molecular Biology Inc
Rights: fechado
Identifier DOI: 10.1074/jbc.M111.283341
Date Issue: 2012
Appears in Collections:Artigos e Materiais de Revistas Científicas - Unicamp

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