Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2000-8-16
pubmed:abstractText
The Src homology (SH) 2 domain adaptor protein Shb has previously been shown to interact with the platelet-derived growth factor (PDGF)-beta receptor. In this study we show an association between Shb and the PDGF-alpha receptor which is mediated by the SH2 domain of Shb and involves tyrosine residue 720 in the kinase insert domain of the receptor. To assess the role of Shb in PDGF-mediated signaling, we have overexpressed wild-type Shb or Shb carrying a mutation (R522K) which renders the SH2 domain inactive, in Patch mouse (PhB) fibroblasts expressing both PDGF receptors (PhB/Ralpha). Overexpression of wild-type Shb, but not the R522K Shb mutant, affected PDGF-mediated reorganization of the cytoskeleton by decreasing membrane ruffle formation and stimulating the generation of filopodia relative the parental control cells. In addition, the PDGF-induced receptor-associated phosphatidylinositol 3'-kinase activity and phosphorylation of Akt was similar in both PhB/Ralpha/Shb and PhB/Ralpha/ShbR522K cells compared with the parental control, whereas the activation of Rac in response to PDGF-BB was diminished only in the PhB/Ralpha/Shb cells. We conclude that Shb plays a role in PDGF-dependent regulation of certain cytoskeletal changes by modulating the ability of PDGF to activate Rac.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Platelet-Derived Growth Factor, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt, http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Platelet-Derived Growth..., http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Platelet-Derived Growth..., http://linkedlifedata.com/resource/pubmed/chemical/Shb protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/platelet-derived growth factor A, http://linkedlifedata.com/resource/pubmed/chemical/platelet-derived growth factor BB, http://linkedlifedata.com/resource/pubmed/chemical/rac GTP-Binding Proteins
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0014-4827
pubmed:author
pubmed:copyrightInfo
Copyright 2000 Academic Press.
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
257
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
245-54
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:10837138-3T3 Cells, pubmed-meshheading:10837138-Amino Acid Sequence, pubmed-meshheading:10837138-Animals, pubmed-meshheading:10837138-Cells, Cultured, pubmed-meshheading:10837138-Cytoskeleton, pubmed-meshheading:10837138-Endothelium, Vascular, pubmed-meshheading:10837138-Enzyme Activation, pubmed-meshheading:10837138-Mice, pubmed-meshheading:10837138-Molecular Sequence Data, pubmed-meshheading:10837138-Phosphatidylinositol 3-Kinases, pubmed-meshheading:10837138-Phosphorylation, pubmed-meshheading:10837138-Platelet-Derived Growth Factor, pubmed-meshheading:10837138-Precipitin Tests, pubmed-meshheading:10837138-Protein Binding, pubmed-meshheading:10837138-Protein-Serine-Threonine Kinases, pubmed-meshheading:10837138-Proto-Oncogene Proteins, pubmed-meshheading:10837138-Proto-Oncogene Proteins c-akt, pubmed-meshheading:10837138-Receptor, Platelet-Derived Growth Factor alpha, pubmed-meshheading:10837138-Receptor, Platelet-Derived Growth Factor beta, pubmed-meshheading:10837138-Signal Transduction, pubmed-meshheading:10837138-Swine, pubmed-meshheading:10837138-rac GTP-Binding Proteins, pubmed-meshheading:10837138-src Homology Domains
pubmed:year
2000
pubmed:articleTitle
Platelet-derived growth factor-mediated signaling through the Shb adaptor protein: effects on cytoskeletal organization.
pubmed:affiliation
Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, S-751 24, Sweden.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't