Linked Life Data

15051508

Source:http://linkedlifedata.com/resource/pubmed/id/15051508

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-3-30
pubmed:abstractText
We have asked whether the Nck and Crk adaptor proteins play important roles in the vascular endothelial growth factor (VEGF)-induced signaling pathways that lead to an enhancement in cell migration. The introduction into human umbilical vein endothelial cells of a dominant-negative inhibitor for either Nck or Crk blocked the recruitment of both endogenous proteins to the KDR VEGF receptor subtype indicating that both proteins are recruited to the same docking site. The Nck and Crk dominant-negatives led to the formation of abnormally large focal adhesion, blocked VEGF-induced integrin activation, and blocked VEGF-induced actin dynamics. The dominant-negatives had no effects on these properties in cells expressing constitutively active Rac1 or RhoA. Since a DN to either Nck or Crk blocks the cellular responses mediated by both proteins, we performed experiments directed at clarifying signaling pathways specifically mediated by each protein. Inhibition of the interaction between Nck with its downstream effector PAK led to abnormally large focal adhesions, but had no effect on integrin activation or cell adhesiveness. Evidence is presented that Crk complexes with C3G in control cells, and VEGF treatment leads to the recruitment of the complex to the cell surface. Inhibition of the C3G downstream effector Rap1 leads to enlarged focal adhesions and blocks VEGF-induced integrin activation. We conclude that Nck and Crk mediate distinct VEGF-induced signaling pathways that serve overlapping functions in cell migration.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0014-4827
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
295
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
258-68
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:15051508-Adaptor Proteins, Signal Transducing, pubmed-meshheading:15051508-Adaptor Proteins, Vesicular Transport, pubmed-meshheading:15051508-Amino Acid Sequence, pubmed-meshheading:15051508-Cell Adhesion, pubmed-meshheading:15051508-Cell Line, pubmed-meshheading:15051508-Cell Movement, pubmed-meshheading:15051508-Endothelium, Vascular, pubmed-meshheading:15051508-Gene Expression Regulation, pubmed-meshheading:15051508-Humans, pubmed-meshheading:15051508-Integrins, pubmed-meshheading:15051508-Molecular Sequence Data, pubmed-meshheading:15051508-Oncogene Proteins, pubmed-meshheading:15051508-Peptide Fragments, pubmed-meshheading:15051508-Proto-Oncogene Proteins c-crk, pubmed-meshheading:15051508-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:15051508-Signal Transduction, pubmed-meshheading:15051508-Umbilical Veins, pubmed-meshheading:15051508-Vascular Endothelial Growth Factor A
pubmed:year
2004
pubmed:articleTitle
Nck and Crk mediate distinct VEGF-induced signaling pathways that serve overlapping functions in focal adhesion turnover and integrin activation.
pubmed:affiliation
Cardiology Division, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.