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The B56 family of protein phosphatase 2A (PP2A) regulatory subunits encodes differentiation-induced phosphoproteins that target PP2A to both nucleus and cytoplasm
被引:330
作者:
McCright, B
Rivers, AM
Audlin, S
Virshup, DM
机构:
[1] UNIV UTAH, SCH MED, DEPT ONCOL SCI, DIV MOL BIOL & GENET, SALT LAKE CITY, UT 84112 USA
[2] UNIV UTAH, SCH MED, PROGRAM HUMAN MOL BIOL & GENET, SALT LAKE CITY, UT 84112 USA
[3] UNIV UTAH, SCH MED, COMBINED PROGRAM MOL BIOL, SALT LAKE CITY, UT 84112 USA
[4] UNIV UTAH, SCH MED, DEPT PEDIAT, SALT LAKE CITY, UT 84112 USA
关键词:
D O I:
10.1074/jbc.271.36.22081
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
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 (B56 gamma 1) are phosphoproteins, as shown by mobility shift after treatment with alkaline phosphatase and metabolic labeling with [P-32]phosphate. All labeled isoforms contain solely phosphoserine. Indirect immunofluorescence microscopy demonstrates distinct patterns of intracellular targeting by different B56 isoforms. Specifically, B56 alpha, B56 beta, and B56 epsilon complexed with the protein phosphatase 2A A and C subunits localize to the cytoplasm, whereas B56 delta, B56 gamma 1, and B56 gamma 3 are concentrated in the nucleus. Two isoforms (B56 beta and B56 delta) are highly expressed in adult brain; here we show that mRNA for these isoforms in creases 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.
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页码:22081 / 22089
页数:9
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