Document Detail


The alpha4-containing form of protein phosphatase 2A in liver and hepatic cells.
MedLine Citation:
PMID:  18543252     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The Ser/Thr phosphatase PP2A is a set of multisubunit enzymes that regulate many cellular processes. In yeast, the PP2A regulatory subunit Tap42 forms part of the target of rapamycin (TOR) signaling pathway that links nutrient and energy availability to cell growth. The physiological intersection between the mammalian orthologs of Tap42 and TOR, alpha4 and mTOR, has not been fully characterized. We used two in vivo models of liver growth in the rat, late gestation fetal development and regeneration after partial hepatectomy, to explore the regulation of the alpha4-containing form of PP2A. The alpha4/PP2A catalytic subunit (alpha4/PP2A-C) complex was present in both fetal and adult liver extracts. There was a trend towards higher levels of alpha4 protein in fetal liver, but the complex was more abundant in adult liver. Fractionation of extracts by ion exchange chromatography and transient transfection of the AML12 mouse hepatic cell line indicated that alpha4 associates with PP2A-C but that these complexes have low catalytic activity with both peptide and protein substrates. alpha4 was able to associate with forms of PP2A-C that were both methylated and non-methylated at the carboxy-terminus. The mTOR inhibitor rapamycin did not block the formation of alpha4/PP2A-C in liver or hepatic cells, nor did it appear to modulate PP2A activity. Furthermore, sensitivity to the growth inhibitory effects of rapamycin among a panel of hepatic cell lines did not correlate with levels of alpha4 or alpha4/PP2A-C. Our results indicate that the yeast Tap42/TOR paradigm is not conserved in hepatic cells.
Authors:
Sunny J-S Yoo; Rosa H Jimenez; Jennifer A Sanders; Joan M Boylan; David L Brautigan; Philip A Gruppuso
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of cellular biochemistry     Volume:  105     ISSN:  1097-4644     ISO Abbreviation:  J. Cell. Biochem.     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-08-28     Completed Date:  2008-10-27     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  8205768     Medline TA:  J Cell Biochem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  290-300     Citation Subset:  IM    
Copyright Information:
(c) 2008 Wiley-Liss, Inc.
Affiliation:
Department of Pediatrics, Rhode Island Hospital and Brown University, Providence, Rhode Island 02903, USA.
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MeSH Terms
Descriptor/Qualifier:
Aging / physiology
Animals
Cell Line
Hepatocytes / drug effects,  enzymology*
Liver / drug effects,  enzymology*
Male
Mice
Protein Phosphatase 2 / genetics,  isolation & purification,  metabolism*
Protein Subunits / metabolism
Rats
Rats, Sprague-Dawley
Sensitivity and Specificity
Sirolimus / pharmacology
Grant Support
ID/Acronym/Agency:
F31HD041893/HD/NICHD NIH HHS; R01 HD024455/HD/NICHD NIH HHS; R01 HD024455-19/HD/NICHD NIH HHS; R01CA77584/CA/NCI NIH HHS; R01HD24455/HD/NICHD NIH HHS; R01HD35831/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Protein Subunits; 53123-88-9/Sirolimus; EC 3.1.3.16/Protein Phosphatase 2
Comments/Corrections

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