Role of the Raf/mitogen-activated protein kinase pathway in p21ras desensitization
UMass Chan Affiliations
Program in Molecular MedicineDocument Type
Journal ArticlePublication Date
1996-07-12Keywords
3T3 Cells*Adaptor Proteins, Signal Transducing
Animals
Enzyme Activation
Epidermal Growth Factor
Estradiol
GRB2 Adaptor Protein
Membrane Proteins
Mice
Phosphorylation
Platelet-Derived Growth Factor
Protein Kinases
Protein-Serine-Threonine Kinases
Proteins
Proto-Oncogene Proteins
Proto-Oncogene Proteins c-raf
Proto-Oncogene Proteins p21(ras)
Receptors, Estradiol
Recombinant Fusion Proteins
Son of Sevenless Proteins
Tetradecanoylphorbol Acetate
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
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).Source
J Biol Chem. 1996 Jul 12;271(28):16674-7.
DOI
10.1074/jbc.271.28.16674Permanent Link to this Item
http://hdl.handle.net/20.500.14038/42446PubMed ID
8663295Related Resources
ae974a485f413a2113503eed53cd6c53
10.1074/jbc.271.28.16674
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