Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 278, Issue 27, Pages 24976-24985Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M302832200
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- NIGMS NIH HHS [GM51366] Funding Source: Medline
- NINDS NIH HHS [NS43254] Funding Source: Medline
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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.
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