Linked Life Data

16046479

Source:http://linkedlifedata.com/resource/pubmed/id/16046479

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 16
pubmed:dateCreated
2005-8-17
pubmed:abstractText
Calmodulin (CaM) is a ubiquitous transducer of intracellular Ca(2+) signals and plays a key role in the regulation of the function of all cells. The interaction of CaM with a specific target is determined not only by the Ca(2+)-dependent affinity of calmodulin but also by the proximity to that target in the cellular environment. Although a few reports of stimulus-dependent nuclear targeting of CaM have appeared, the mechanisms by which CaM is targeted to non-nuclear sites are less clear. Here, we investigate the hypothesis that MARCKS is a regulator of the spatial distribution of CaM within the cytoplasm of differentiated smooth-muscle cells. In overlay assays with portal-vein homogenates, CaM binds predominantly to the MARCKS-containing band. MARCKS is abundant in portal-vein smooth muscle ( approximately 16 microM) in comparison to total CaM ( approximately 40 microM). Confocal images indicate that calmodulin and MARCKS co-distribute in unstimulated freshly dissociated smooth-muscle cells and are co-targeted simultaneously to the cell interior upon depolarization. Protein-kinase-C (PKC) activation triggers a translocation of CaM that precedes that of MARCKS and causes multisite, sequential MARCKS phosphorylation. MARCKS immunoprecipitates with CaM in a stimulus-dependent manner. A synthetic MARCKS effector domain (ED) peptide labelled with a photoaffinity probe cross-links CaM in smooth-muscle tissue in a stimulus-dependent manner. Both cross-linking and immunoprecipitation increase with increased Ca(2+) concentration, but decrease with PKC activation. Introduction of a nonphosphorylatable MARCKS decoy peptide blocks the PKC-mediated targeting of CaM. These results indicate that MARCKS is a significant, PKC-releasable reservoir of CaM in differentiated smooth muscle and that it contributes to CaM signalling by modulating the intracellular distribution of CaM.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0021-9533
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
118
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3595-605
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:16046479-Animals, pubmed-meshheading:16046479-Calcium, pubmed-meshheading:16046479-Calcium Signaling, pubmed-meshheading:16046479-Calmodulin, pubmed-meshheading:16046479-Cells, Cultured, pubmed-meshheading:16046479-Cytoplasm, pubmed-meshheading:16046479-Enzyme Inhibitors, pubmed-meshheading:16046479-Ferrets, pubmed-meshheading:16046479-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:16046479-Membrane Potentials, pubmed-meshheading:16046479-Membrane Proteins, pubmed-meshheading:16046479-Muscle, Smooth, Vascular, pubmed-meshheading:16046479-Muscle Contraction, pubmed-meshheading:16046479-Myocytes, Smooth Muscle, pubmed-meshheading:16046479-Peptides, pubmed-meshheading:16046479-Phosphorylation, pubmed-meshheading:16046479-Protein Binding, pubmed-meshheading:16046479-Protein Kinase C, pubmed-meshheading:16046479-Protein Transport
pubmed:year
2005
pubmed:articleTitle
MARCKS is a major PKC-dependent regulator of calmodulin targeting in smooth muscle.
pubmed:affiliation
Boston Biomedical Research Institute, 64 Grove Street, Watertown, MA 02472, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, N.I.H., Extramural