RGD Reference Report - A developmentally regulated, neuron-specific splice variant of the variable subunit Bbeta targets protein phosphatase 2A to mitochondria and modulates apoptosis. - Rat Genome Database

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A developmentally regulated, neuron-specific splice variant of the variable subunit Bbeta targets protein phosphatase 2A to mitochondria and modulates apoptosis.

Authors: Dagda, RK  Zaucha, JA  Wadzinski, BE  Strack, S 
Citation: Dagda RK, etal., J Biol Chem. 2003 Jul 4;278(27):24976-85. Epub 2003 Apr 24.
RGD ID: 2314541
Pubmed: (View Article at PubMed) PMID:12716901
DOI: Full-text: DOI:10.1074/jbc.M302832200

Heterotrimeric protein phosphatase 2A (PP2A) is a major Ser/Thr phosphatase composed of catalytic, structural, and regulatory subunits. Here, we characterize Bbeta2, a novel splice variant of the neuronal Bbeta regulatory subunit with a unique N-terminal tail. Bbeta2 is expressed predominantly in forebrain areas, and PP2A holoenzymes containing Bbeta2 are about 10-fold less abundant than those containing the Bbeta1 (previously Bbeta) isoform. Bbeta2 mRNA is dramatically induced postnatally and in response to neuronal differentiation of a hippocampal progenitor cell line. The divergent N terminus of Bbeta2 does not affect phosphatase activity but encodes a subcellular targeting signal. Bbeta2, but not Bbeta1 or an N-terminal truncation mutant, colocalizes with mitochondria in neuronal PC12 cells. Moreover, the Bbeta2 N-terminal tail is sufficient to target green fluorescent protein to this organelle. Inducible or transient expression of Bbeta2, but neither Bbeta1, Bgamma, nor a Bbeta2 mutant defective in holoenzyme formation, accelerates apoptosis in response to growth factor deprivation. Thus, alternative splicing of a mitochondrial localization signal generates a PP2A holoenzyme involved in neuronal survival signaling.

Annotation

Gene Ontology Annotations    

Cellular Component

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Ppp2r2b  (protein phosphatase 2, regulatory subunit B, beta)


Additional Information