SOS-mediated nucleotide exchange of RAS (mediated by GRB2:SOS1 in complex with ligand-responsive p-6Y-EGFR mutants)

Stable Identifier
R-HSA-1225951
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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Based on the wild-type EGFR signaling, it is assumed that the guanine nucleotide exchange factor SOS1 interacts with phosphorylated EGFR mutants through the adaptor protein, GRB2. Upon formation of this complex, SOS1 activates RAS by promoting GDP release and GTP binding. Although this reaction has not been directly confirmed for EGFR cancer mutants, activation of RAF/MAP kinase cascade has been demonstrated, through detection of phosphorylated ERK1/2, in cells expressing EGFR L858R mutant (Sordella et al. 2004, Paez et al. 2004, Shimamura et al. 2005), EGFR E746_A750del mutant (Sordella et al. 2004, Shimamura et al. 2005), EGFR L747_P753delinsS mutant (Sordella et al. 2004) and EGFR E746_A750del;T790M double mutant (Shimamura et al. 2005).

Literature References
PubMed ID Title Journal Year
15284455 Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways

Sordella, R, Bell, DW, Haber, DA, Settleman, J

Science 2004
15118125 EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy

Paez, JG, Jänne, PA, Lee, JC, Tracy, S, Greulich, H, Gabriel, S, Herman, P, Kaye, FJ, Lindeman, N, Boggon, TJ, Naoki, K, Sasaki, H, Fujii, Y, Eck, MJ, Sellers, WR, Johnson, BE, Meyerson, M

Science 2004
16024644 Epidermal growth factor receptors harboring kinase domain mutations associate with the heat shock protein 90 chaperone and are destabilized following exposure to geldanamycins

Shimamura, T, Lowell, AM, Engelman, JA, Shapiro, GI

Cancer Res 2005
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
Ras guanyl-nucleotide exchange factor activity of Ligand-responsive p-6Y-EGFR mutants:GRB2:SOS1 [plasma membrane]
Physical Entity
Activity
Normal reaction
Disease
Name Identifier Synonyms
cancer 162 malignant tumor, malignant neoplasm, primary cancer
Authored
Reviewed
Created