Linked Life Data

14596793

Source:http://linkedlifedata.com/resource/pubmed/id/14596793

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2003-11-4
pubmed:abstractText
cAMP-dependent protein kinase (PKA)-dependent phosphorylation of the two serine residues in the amino terminal region unique to cardiac troponin I (cTnI) is known to cause two effects: (i) decrease of the maximum Ca2+-controlled thin filament-activated myosin S1-ATPase (actoS1-ATPase) activity and mean sliding velocity of reconstituted thin filaments; (ii) rightward shift of the Ca2+ activation curves of actoS1-ATPase activity, filament sliding velocity, and force generation. We have studied the influence of phosphorylation of human wild-type cTnI and of two mutant cTnI (G203S and K206Q) causing familial hypertrophic cardiomyopathy (fHCM) on the secondary structure by circular dichroism spectroscopy and on the Ca2+ regulation of actin-myosin interaction using actoS1-ATPase activity and in vitro motility assays. Both mutations slightly influence the backbone structure of cTnI but only the secondary structure of cTnI-G203S is also affected by bis-phosphorylation of cTnI. In functional studies, cTnI-G203S behaves similarly to wild-type cTnI, i.e. the mutation itself has no measurable effect and bis-phosphorylation alters the actoS1-ATPase activity and the in vitro thin filament motility in the same way as does bis-phosphorylation of wild-type cTnI. In contrast, the mutation K206Q leads to a considerable increase in the maximum actoS1-ATPase activity as well as filament motility compared to wild-type cTnI. Bis-phosphorylation of this mutant cTnI still suppresses the maximum actoS1-ATPase activity and filament sliding velocity but does no longer affect the Ca2+ sensitivity of these processes. Thus, these two fHCM-linked cTnI mutations, although reflecting similar pathological situations, exert different effects on the actomyosin system per se and in response to bis-phosphorylation of cTnI.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-2828
pubmed:author
pubmed:issnType
Print
pubmed:volume
35
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1365-74
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:14596793-Actin Cytoskeleton, pubmed-meshheading:14596793-Actomyosin, pubmed-meshheading:14596793-Adenosine Triphosphatases, pubmed-meshheading:14596793-Animals, pubmed-meshheading:14596793-Antibodies, Monoclonal, pubmed-meshheading:14596793-Calcium, pubmed-meshheading:14596793-Cardiomyopathy, Hypertrophic, Familial, pubmed-meshheading:14596793-Circular Dichroism, pubmed-meshheading:14596793-Humans, pubmed-meshheading:14596793-Mutagenesis, Site-Directed, pubmed-meshheading:14596793-Mutation, Missense, pubmed-meshheading:14596793-Myocardium, pubmed-meshheading:14596793-Phosphorylation, pubmed-meshheading:14596793-Protein Structure, Secondary, pubmed-meshheading:14596793-Rabbits, pubmed-meshheading:14596793-Recombinant Proteins, pubmed-meshheading:14596793-Serine, pubmed-meshheading:14596793-Troponin I
pubmed:year
2003
pubmed:articleTitle
Phosphorylation of human cardiac troponin I G203S and K206Q linked to familial hypertrophic cardiomyopathy affects actomyosin interaction in different ways.
pubmed:affiliation
St. Josef-Hospital, Klinik der Ruhr-Universität Bochum, Gudrunstrasse 56, 44791 Bochum, Germany.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't