The B56 Family of Protein Phosphatase 2A (PP2A) Regulatory Subunits Encodes Differentiation-induced Phosphoproteins That Target PP2A to Both Nucleus and Cytoplasm
Open Access
- 1 September 1996
- journal article
- Published by Elsevier BV in Journal of Biological Chemistry
- Vol. 271 (36), 22081-22089
- https://doi.org/10.1074/jbc.271.36.22081
Abstract
Protein phosphatase 2A is a heterotrimeric protein serine/threonine phosphatase consisting of a 36-kDa catalytic C subunit, a 65-kDa structural A subunit, and a variable regulatory B subunit. The B subunits determine the substrate specificity of the enzyme. There have been three families of cellular B subunits identified to date: B55, B56 (B′), and PR72/130. We have now cloned five genes encoding human B56 isoforms. Polypeptides encoded by all but one splice variant (B56γ1) are phosphoproteins, as shown by mobility shift after treatment with alkaline phosphatase and metabolic labeling with [32P]phosphate. All labeled isoforms contain solely phosphoserine. Indirect immunofluorescence microscopy demonstrates distinct patterns of intracellular targeting by different B56 isoforms. Specifically, B56α, B56β, and B56ε complexed with the protein phosphatase 2A A and C subunits localize to the cytoplasm, whereas B56δ, B56γ1, and B56γ3 are concentrated in the nucleus. Two isoforms (B56β and B56δ) are highly expressed in adult brain; here we show that mRNA for these isoforms increases severalfold when neuroblastoma cell lines are induced to differentiate by retinoic acid treatment. These studies demonstrate an increasing diversity of regulatory mechanisms to control the activity of this key intracellular protein phosphatase and suggest distinct functions for isoforms targeted to different intracellular locations.Keywords
This publication has 35 references indexed in Scilit:
- High Complexity in the Expression of the B′ Subunit of Protein Phosphatase 2A0Published by Elsevier BV ,1996
- Molecular cloning of a 74‐kDa regulatory subunit (B″ or δ) of human protein phosphatase 2AFEBS Letters, 1996
- Identification of a New Family of Protein Phosphatase 2A Regulatory SubunitsJournal of Biological Chemistry, 1995
- Association of Protein Kinase A and Protein Phosphatase 2B with a Common Anchoring ProteinScience, 1995
- Protein phosphatase 2A — a ‘ménage à trois’Trends in Cell Biology, 1994
- The interaction of SV40 small tumor antigen with protein phosphatase 2A stimulates the map kinase pathway and induces cell proliferationCell, 1993
- dbEST — database for “expressed sequence tags”Nature Genetics, 1993
- The 55 kd regulatory subunit of Drosophila protein phosphatase 2A is required for anaphaseCell, 1993
- Basic local alignment search toolJournal of Molecular Biology, 1990
- The structure of an antigenic determinant in a proteinCell, 1984