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Identification and Characterization of an Alternatively Spliced Isoform of the Human Protein Phosphatase 2Aα Catalytic Subunit
Author(s) -
Smetana Juliana H C,
Migueleti Deivid L,
Nunes Hugo F,
Kobarg Jörg,
Zanchin Nilson I
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.lb181
Subject(s) - protein subunit , protein phosphatase 2 , gene isoform , phosphatase , messenger rna , microbiology and biotechnology , serine , chemistry , biochemistry , biology , gene , enzyme
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, allowing for the assembly of more than 70 different holoenzymes. The catalytic subunit can also interact with α4, TIPRL, 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. 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 outcompetes 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.