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dc.contributor.authorKlarlund, Jes K.
dc.contributor.authorCherniack, Andrew D.
dc.contributor.authorMcMahon, Martin
dc.contributor.authorCzech, Michael P.
dc.date2022-08-11T08:10:04.000
dc.date.accessioned2022-08-23T16:54:12Z
dc.date.available2022-08-23T16:54:12Z
dc.date.issued1996-07-12
dc.date.submitted2008-08-15
dc.identifier.citation<p>J Biol Chem. 1996 Jul 12;271(28):16674-7.</p>
dc.identifier.issn0021-9258 (Print)
dc.identifier.doi10.1074/jbc.271.28.16674
dc.identifier.pmid8663295
dc.identifier.urihttp://hdl.handle.net/20.500.14038/42446
dc.description.abstractDesensitization of p21(ras) after stimulation of cells by growth factors and phorbol 12-myristate 13-acetate (PMA) correlates with hyperphosphorylation of the guanine nucleotide exchange factor Son-of-sevenless (Sos) and its dissociation from the adaptor protein Grb2 (Cherniack, A., Klarlund, J. K., Conway, B. R., and Czech, M. P. (1995) J. Biol. Chem. 270, 1485-1488). To test the role of the Raf/mitogen-activated protein (MAP) kinase pathway, we utilized cells expressing a chimera composed of the catalytic domain of p74Raf-1 and the hormone binding domain of the estradiol receptor (DeltaRaf-1:ER). Estradiol markedly stimulated DeltaRaf-1:ER and the downstream MEK and MAP kinases in these cells as well as Sos phosphorylation. However, the dissociation of Grb2 from Sos observed in response to PMA was not apparent upon DeltaRaf-1:ER activation. Furthermore, stimulation of DeltaRaf-1:ER did not impair GTP loading of p21(ras) in response to platelet-derived growth factor or epidermal growth factor. We conclude that activation of the Raf/MAP kinase pathway alone in these cells is insufficient to cause disassembly of Sos from Grb2 or to interrupt the ability of Sos to catalyze activation of p21(ras).
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=8663295&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://doi.org/10.1074/jbc.271.28.16674
dc.subject3T3 Cells
dc.subject*Adaptor Proteins, Signal Transducing
dc.subjectAnimals
dc.subjectEnzyme Activation
dc.subjectEpidermal Growth Factor
dc.subjectEstradiol
dc.subjectGRB2 Adaptor Protein
dc.subjectMembrane Proteins
dc.subjectMice
dc.subjectPhosphorylation
dc.subjectPlatelet-Derived Growth Factor
dc.subjectProtein Kinases
dc.subjectProtein-Serine-Threonine Kinases
dc.subjectProteins
dc.subjectProto-Oncogene Proteins
dc.subjectProto-Oncogene Proteins c-raf
dc.subjectProto-Oncogene Proteins p21(ras)
dc.subjectReceptors, Estradiol
dc.subjectRecombinant Fusion Proteins
dc.subjectSon of Sevenless Proteins
dc.subjectTetradecanoylphorbol Acetate
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleRole of the Raf/mitogen-activated protein kinase pathway in p21ras desensitization
dc.typeArticle
dc.source.journaltitleThe Journal of biological chemistry
dc.source.volume271
dc.source.issue28
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/795
dc.identifier.contextkey579679
html.description.abstract<p>Desensitization of p21(ras) after stimulation of cells by growth factors and phorbol 12-myristate 13-acetate (PMA) correlates with hyperphosphorylation of the guanine nucleotide exchange factor Son-of-sevenless (Sos) and its dissociation from the adaptor protein Grb2 (Cherniack, A., Klarlund, J. K., Conway, B. R., and Czech, M. P. (1995) J. Biol. Chem. 270, 1485-1488). To test the role of the Raf/mitogen-activated protein (MAP) kinase pathway, we utilized cells expressing a chimera composed of the catalytic domain of p74Raf-1 and the hormone binding domain of the estradiol receptor (DeltaRaf-1:ER). Estradiol markedly stimulated DeltaRaf-1:ER and the downstream MEK and MAP kinases in these cells as well as Sos phosphorylation. However, the dissociation of Grb2 from Sos observed in response to PMA was not apparent upon DeltaRaf-1:ER activation. Furthermore, stimulation of DeltaRaf-1:ER did not impair GTP loading of p21(ras) in response to platelet-derived growth factor or epidermal growth factor. We conclude that activation of the Raf/MAP kinase pathway alone in these cells is insufficient to cause disassembly of Sos from Grb2 or to interrupt the ability of Sos to catalyze activation of p21(ras).</p>
dc.identifier.submissionpathoapubs/795
dc.contributor.departmentProgram in Molecular Medicine
dc.source.pages16674-7


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