SOS-mediated nucleotide exchange of RAS (mediated by GRB2:SOS1 in complex with phosphorylated SHC1 and ligand-responsive p-6Y-EGFR mutants)

Stable Identifier
R-HSA-1225957
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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SOS1 is the guanine nucleotide exchange factor (GEF) for RAS. SOS1, recruited by GRB2 bound to p-SHC1:p-EGFR mutants, is assumed to activate RAS nucleotide exchange from the inactive form (bound to GDP) to an active form (bound to GTP). Although this reaction has not been shown to occur directly for EGFR cancer mutants, activation of RAF/MAP kinase cascade, through detection of phosphorylated ERK1/2, has been demonstrated in cells expressing EGFR L858R mutant (Sordella et al. 2004, Paez et al. 2004, Shimamura et al. 2005), EGFR E746_A750 mutant (Sordella et al. 2004, Shimamura et al. 2005), EGFR L747_P753delinS 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:p-Y349,350-SHC1:GRB2:SOS1 [plasma membrane]
Physical Entity
Activity
Normal reaction
Disease
Name Identifier Synonyms
cancer 162 malignant tumor, malignant neoplasm, primary cancer
Authored
Reviewed
Created