Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-2-12
pubmed:abstractText
The regulation of small artery contractility by vasoconstrictors is important for vascular function, and actin cytoskeleton remodeling is required for contraction. p38 MAPK and tyrosine kinases are implicated in actin polymerization and contraction through heat shock protein 27 (Hsp27) and the cytoskeletal protein paxillin, respectively. We evaluated the roles of downstream targets of p38 MAPK and tyrosine kinases in cytoskeletal reorganization and contraction and whether the two signaling pathways regulate contraction independent of each other. We identified the expression of the paxillin homologue hydrogen peroxide-inducible clone-5 (Hic-5) and showed its activation by norepinephrine (NE) in a Src-dependent manner. Furthermore, we demonstrated a NE-induced interaction of proline-rich tyrosine kinase-2 (PYK2) but not Src or p125 focal adhesion kinase with Hic-5. This interaction was Src dependent, suggesting that Hic-5 was a substrate for PYK2 downstream from Src. The activation of Hic-5 induced its relocalization to the cytosol. The parallel activation of Hsp27 by NE was p38 MAPK dependent and led to its dissociation from actin filaments and translocation from membrane to cytosol and increased actin polymerization. Both Hsp27 and Hic-5 activation resulted in their association within the same time frame as NE-induced contraction, and the inhibition of either p38 MAPK or Src inhibited the interaction between Hsp27 and Hic-5 and the contractile response. Furthermore, combined p38 MAPK and Src inhibition had no greater effect on contraction than individual inhibition, suggesting that the two pathways act through a common mechanism. These data show that NE-induced activation and the association of Hsp27 and Hic-5 are required for the reorganization of the actin cytoskeleton and force development in small arteries.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Actins, http://linkedlifedata.com/resource/pubmed/chemical/Cytoskeletal Proteins, http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/HSP27 Heat-Shock Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Heat-Shock Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Hspb1 protein, rat, http://linkedlifedata.com/resource/pubmed/chemical/Hydrogen Peroxide, http://linkedlifedata.com/resource/pubmed/chemical/LIM Domain Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Norepinephrine, http://linkedlifedata.com/resource/pubmed/chemical/Oxidants, http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatases..., http://linkedlifedata.com/resource/pubmed/chemical/Tgfb1i1 protein, rat, http://linkedlifedata.com/resource/pubmed/chemical/Vasoconstrictor Agents, http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein..., http://linkedlifedata.com/resource/pubmed/chemical/src-Family Kinases
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0363-6135
pubmed:author
pubmed:issnType
Print
pubmed:volume
294
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
H961-9
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:18083901-Actins, pubmed-meshheading:18083901-Animals, pubmed-meshheading:18083901-Blotting, Western, pubmed-meshheading:18083901-Cytoskeletal Proteins, pubmed-meshheading:18083901-DNA-Binding Proteins, pubmed-meshheading:18083901-Enzyme Inhibitors, pubmed-meshheading:18083901-HSP27 Heat-Shock Proteins, pubmed-meshheading:18083901-Heat-Shock Proteins, pubmed-meshheading:18083901-Hydrogen Peroxide, pubmed-meshheading:18083901-Immunoprecipitation, pubmed-meshheading:18083901-LIM Domain Proteins, pubmed-meshheading:18083901-Mesenteric Arteries, pubmed-meshheading:18083901-Muscle, Smooth, Vascular, pubmed-meshheading:18083901-Muscle Contraction, pubmed-meshheading:18083901-Neoplasm Proteins, pubmed-meshheading:18083901-Norepinephrine, pubmed-meshheading:18083901-Oxidants, pubmed-meshheading:18083901-Phosphorylation, pubmed-meshheading:18083901-Protein Tyrosine Phosphatases, Non-Receptor, pubmed-meshheading:18083901-Rats, pubmed-meshheading:18083901-Rats, Sprague-Dawley, pubmed-meshheading:18083901-Subcellular Fractions, pubmed-meshheading:18083901-Vasoconstrictor Agents, pubmed-meshheading:18083901-p38 Mitogen-Activated Protein Kinases, pubmed-meshheading:18083901-src-Family Kinases
pubmed:year
2008
pubmed:articleTitle
Regulation of contractility by Hsp27 and Hic-5 in rat mesenteric small arteries.
pubmed:affiliation
Cardiovascular Research Group, University of Manchester, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't