Linked Life Data

12614145

Source:http://linkedlifedata.com/resource/pubmed/id/12614145

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2003-3-4
pubmed:abstractText
Smooth muscle caldesmon (CaD) binds F-actin and inhibits actomyosin ATPase activity. The inhibition is reversed by Ca2+/calmodulin (CaM). CaD is also phosphorylated upon stimulation at sites specific for mitogen-activated protein kinases (MAPKs). Because of these properties, CaD is thought to be involved in the regulation of smooth muscle contraction. The molecular mechanism of the reversal of inhibition is not well understood. We have expressed His6-tagged fragments containing the sequence of the C-terminal region of human (from M563 to V793) and chicken (from M563 to P771) CaD as well as a variant of the chicken isoform with a Q766C point mutation. By cleavages with proteases, followed by high-speed cosedimentation with F-actin and mass spectrometry, we found that within the C-terminal region of CaD there are multiple actin contact points forming two clusters. Intramolecular fluorescence resonance energy transfer between probes attached to cysteine residues (the endogenous C595 and the engineered C766) located in these two clusters revealed that the C-terminal region of CaD is elongated, but it becomes more compact when bound to actin. Binding of CaM restores the elongated conformation and facilitates dissociation of the C-terminal CaD fragment from F-actin. When the CaD fragment was phosphorylated with a MAPK, only one of the two actin-binding clusters dissociated from F-actin, whereas the other remained bound. Taken together, these results demonstrate that while both Ca2+/CaM and MAPK phosphorylation govern CaD's function via a conformational change, the regulatory mechanisms are different.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
11
pubmed:volume
42
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2513-23
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:12614145-Actins, pubmed-meshheading:12614145-Actomyosin, pubmed-meshheading:12614145-Adenosine Triphosphatases, pubmed-meshheading:12614145-Amino Acid Sequence, pubmed-meshheading:12614145-Animals, pubmed-meshheading:12614145-Binding Sites, pubmed-meshheading:12614145-Calcium, pubmed-meshheading:12614145-Calmodulin, pubmed-meshheading:12614145-Calmodulin-Binding Proteins, pubmed-meshheading:12614145-Chickens, pubmed-meshheading:12614145-Fluorescence Resonance Energy Transfer, pubmed-meshheading:12614145-Humans, pubmed-meshheading:12614145-Mitogen-Activated Protein Kinase 1, pubmed-meshheading:12614145-Molecular Sequence Data, pubmed-meshheading:12614145-Phosphorylation, pubmed-meshheading:12614145-Protein Binding, pubmed-meshheading:12614145-Protein Conformation, pubmed-meshheading:12614145-Rabbits, pubmed-meshheading:12614145-Spectrometry, Mass, Matrix-Assisted Laser...
pubmed:year
2003
pubmed:articleTitle
Caldesmon binding to actin is regulated by calmodulin and phosphorylation via different mechanisms.
pubmed:affiliation
Muscle and Motility Group, Boston Biomedical Research Institute, 64 Grove Street, Watertown, Massachusetts 02472, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.