Linked Life Data

12135494

Source:http://linkedlifedata.com/resource/pubmed/id/12135494

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
2002-7-23
pubmed:abstractText
The calcineurin (CaN) alpha and beta catalytic subunit isoforms are coexpressed within almost all cell types. The enzymatic properties of CaN heterodimers comprised of the regulatory B subunit (CnB) with either the alpha or beta catalytic subunit were compared using in vitro phosphatase assays. CaN containing the alpha isoform (CnA alpha) has lower K(m) and higher V(max) values than CaN containing the beta isoform (CnA beta) toward the PO4-RII, PO4-DARPP-32(20-38) peptides, and p-nitrophenylphosphate (pNPP). CaN heterodimers containing the alpha or beta catalytic subunit isoform displayed identical calmodulin dissociation rates. Similar inhibition curves for each CaN heterodimer were obtained with the CaN autoinhibitory peptide (CaP) and cyclophilin A/cyclosporin A (CyPA/CsA) using each peptide substrate at K(m) concentrations, except for a five- to ninefold higher IC50 value measured for CaN containing the beta isoform with p-nitrophenylphosphate as substrate. No difference in stimulation of phosphatase activity toward p-nitrophenylphosphate by FKBP12/FK506 was observed. At low concentrations of FKBP12/FK506, CaN containing the alpha isoform is more sensitive to inhibition than CaN containing the beta isoform using the phosphopeptide substrates. Higher concentrations of FKBP12/FK506 are required for maximal inhibition of beta CaN using PO4-DARPP-32(20-38) as substrate. The functional differences conferred upon CaN by the alpha or beta catalytic subunit isoforms suggest that the alpha:beta and CaN:substrate ratios may determine the levels of CaN phosphatase activity toward specific substrates within tissues and specific cell types. These findings also indicate that the alpha and beta catalytic subunit isoforms give rise to substrate-dependent differences in sensitivity toward FKBP12/FK506.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Cain protein, rat, http://linkedlifedata.com/resource/pubmed/chemical/Calcineurin, http://linkedlifedata.com/resource/pubmed/chemical/Calmodulin, http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Cyclosporine, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes, http://linkedlifedata.com/resource/pubmed/chemical/Nitrophenols, http://linkedlifedata.com/resource/pubmed/chemical/Organophosphorus Compounds, http://linkedlifedata.com/resource/pubmed/chemical/Protein Subunits, http://linkedlifedata.com/resource/pubmed/chemical/Tacrolimus, http://linkedlifedata.com/resource/pubmed/chemical/Tacrolimus Binding Protein 1A, http://linkedlifedata.com/resource/pubmed/chemical/nitrophenylphosphate
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0014-2956
pubmed:author
pubmed:issnType
Print
pubmed:volume
269
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3540-8
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Substrate selectivity and sensitivity to inhibition by FK506 and cyclosporin A of calcineurin heterodimers composed of the alpha or beta catalytic subunit.
pubmed:affiliation
Department of Physiology & Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA. perrino@physio.unr.edu
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't