Linked Life Data

17082196

Source:http://linkedlifedata.com/resource/pubmed/id/17082196

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2007-2-12
pubmed:abstractText
Vasodilator-stimulated phosphoprotein (VASP) is an actin regulatory protein that links signaling pathways to remodeling of the cytoskeleton. VASP functions are modulated by protein kinases, which phosphorylate the sites Ser-157, Ser-239, and Thr-278. The kinase responsible for Thr-278 phosphorylation, biological functions of the phosphorylation, and association with disease states have remained enigmatic. Using VASP phosphorylation status-specific antibodies, we identified AMP-activated protein kinase (AMPK), a serine-threonine kinase and fundamental sensor of energy homeostasis, in a screen for kinases that phosphorylate the Thr-278 site of VASP in endothelial cells. Pharmacological AMPK inhibitors and activators and AMPK mutants revealed that the kinase specifically targets residue Thr-278 but not Ser-157 or Ser-239. Quantitative fluorescence-activated cell sorter analysis and serum response factor transcriptional reporter assays, which quantify the cellular F-/G-actin equilibrium, indicated that AMPK-mediated VASP phosphorylation impaired actin stress fiber formation and altered cell morphology. In the Zucker Diabetic Fatty (ZDF) rat model for type II diabetes, AMPK activity and Thr-278 phosphorylation were substantially reduced in arterial vessel walls. These findings suggest that VASP is a new AMPK substrate, that VASP Thr-278 phosphorylation translates metabolic signals into actin cytoskeleton rearrangements, and that this signaling system becomes down-regulated in diabetic vessels.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
16
pubmed:volume
282
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4601-12
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:17082196-AMP-Activated Protein Kinases, pubmed-meshheading:17082196-Animals, pubmed-meshheading:17082196-Cell Adhesion Molecules, pubmed-meshheading:17082196-Cytoskeleton, pubmed-meshheading:17082196-Diabetes Mellitus, Experimental, pubmed-meshheading:17082196-Diabetes Mellitus, Type 2, pubmed-meshheading:17082196-Endothelial Cells, pubmed-meshheading:17082196-Humans, pubmed-meshheading:17082196-Male, pubmed-meshheading:17082196-Microfilament Proteins, pubmed-meshheading:17082196-Multienzyme Complexes, pubmed-meshheading:17082196-Phosphoproteins, pubmed-meshheading:17082196-Phosphorylation, pubmed-meshheading:17082196-Protein Kinase Inhibitors, pubmed-meshheading:17082196-Protein Processing, Post-Translational, pubmed-meshheading:17082196-Protein-Serine-Threonine Kinases, pubmed-meshheading:17082196-Rats, pubmed-meshheading:17082196-Rats, Zucker, pubmed-meshheading:17082196-Signal Transduction, pubmed-meshheading:17082196-Stress Fibers, pubmed-meshheading:17082196-Substrate Specificity
pubmed:year
2007
pubmed:articleTitle
AMP-activated protein kinase impairs endothelial actin cytoskeleton assembly by phosphorylating vasodilator-stimulated phosphoprotein.
pubmed:affiliation
Institute for Clinical Biochemistry and Pathobiochemistry, Julius-Maximilians-University Würzburg, Josef-Schneider Strasse 2, D-97080 Würzburg, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't