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rdf:type |
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lifeskim:mentions |
umls-concept:C0001511,
umls-concept:C0007634,
umls-concept:C0021665,
umls-concept:C0026882,
umls-concept:C0037083,
umls-concept:C0041485,
umls-concept:C0140080,
umls-concept:C1158478,
umls-concept:C1622501,
umls-concept:C1705422,
umls-concept:C1710082
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pubmed:issue |
9
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pubmed:dateCreated |
2005-2-28
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pubmed:abstractText |
The scaffolding protein receptor for activated C kinase (RACK1) has been proposed to mediate the integration of insulin-like growth factor I receptor (IGF-IR) and adhesion signaling. Here we investigated the mechanism of this integration of signaling, by using an IGF-IR mutant (Y1250F/Y1251F) that is deficient in anti-apoptotic and transforming function. RACK1 was found to associate with the IGF-IR only in adherent cells and did not associate with the IGF-IR in nonadherent cells, lymphocytic cells, or cells expressing the Y1250F/Y1251F mutant. In R- cells transiently expressing the Y1250F/Y1251F mutant RACK1 became constitutively associated with beta1 integrin and did not associate with Shc, Src, or Shp2. This was accompanied by the loss of formation of a complex containing the IGF-IR, RACK1, and beta1 integrin; loss of migratory capacity; enhanced Src and FAK activity; enhanced Akt phosphorylation; and decreased p38 mitogen-activated protein kinase activity. Shc was not phosphorylated in response to IGF-I in cells expressing the Y1250F/Y1251F mutant and remained associated with protein phosphatase 2A. Similar alterations in signaling were observed in cells that were stimulated with IGF-I in nonadherent cultures. Our data suggest that disruption of RACK1 scaffolding function in cells expressing the Y1250F/Y1251F mutant results in the loss of adhesion signals that are necessary to regulate Akt activity and to promote turnover of focal adhesions and cell migration.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD29,
http://linkedlifedata.com/resource/pubmed/chemical/Fibronectins,
http://linkedlifedata.com/resource/pubmed/chemical/GNB2L1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor I,
http://linkedlifedata.com/resource/pubmed/chemical/JNK Mitogen-Activated Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoprotein Phosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Phosphatase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
4
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pubmed:volume |
280
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
7624-33
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15611085-Animals,
pubmed-meshheading:15611085-Antigens, CD29,
pubmed-meshheading:15611085-Blotting, Western,
pubmed-meshheading:15611085-Cell Adhesion,
pubmed-meshheading:15611085-Cell Line,
pubmed-meshheading:15611085-Cell Line, Tumor,
pubmed-meshheading:15611085-Cell Movement,
pubmed-meshheading:15611085-Fibronectins,
pubmed-meshheading:15611085-GTP-Binding Proteins,
pubmed-meshheading:15611085-Humans,
pubmed-meshheading:15611085-Immunoprecipitation,
pubmed-meshheading:15611085-Insulin-Like Growth Factor I,
pubmed-meshheading:15611085-JNK Mitogen-Activated Protein Kinases,
pubmed-meshheading:15611085-Mice,
pubmed-meshheading:15611085-Models, Biological,
pubmed-meshheading:15611085-Mutation,
pubmed-meshheading:15611085-Neoplasm Proteins,
pubmed-meshheading:15611085-Phosphoprotein Phosphatases,
pubmed-meshheading:15611085-Phosphorylation,
pubmed-meshheading:15611085-Protein Binding,
pubmed-meshheading:15611085-Protein Phosphatase 2,
pubmed-meshheading:15611085-Receptors, Cell Surface,
pubmed-meshheading:15611085-Recombinant Proteins,
pubmed-meshheading:15611085-Signal Transduction,
pubmed-meshheading:15611085-Time Factors,
pubmed-meshheading:15611085-Tyrosine,
pubmed-meshheading:15611085-p38 Mitogen-Activated Protein Kinases
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pubmed:year |
2005
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pubmed:articleTitle |
RACK1-mediated integration of adhesion and insulin-like growth factor I (IGF-I) signaling and cell migration are defective in cells expressing an IGF-I receptor mutated at tyrosines 1250 and 1251.
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pubmed:affiliation |
Cell Biology Laboratory, Department of Biochemistry, BioSciences Institute, National University of Ireland, Cork, Ireland.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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