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
cytosol, plasma membrane, extracellular region
ReviewStatus
5/5
Locations in the PathwayBrowser
Expand all
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
SOS-mediated nucleotide exchange of RAS (mediated by GRB2:SOS1 in complex with ligand-responsive p-6Y-EGFR mutants)
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
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
15118125 EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy

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

Science 2004
15284455 Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways

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

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, Shapiro, GI, Engelman, JA

Cancer Res 2005
Participants
Input
Output
Participates
as an event of
Catalyst Activity

guanyl-nucleotide exchange factor activity of Ligand-responsive p-6Y-EGFR mutants:GRB2:SOS1 [plasma membrane]

Physical Entity
Ligand-responsive p-6Y-EGFR mutants:GRB2:SOS1 [plasma membrane] (Homo sapiens)
Activity
guanyl-nucleotide exchange factor activity (GO:0005085)
Normal reaction
SOS1-mediated nucleotide exchange of RAS (EGF:EGFR:GRB2:SOS1) (Homo sapiens)
Functional status

Gain of function of Ligand-responsive p-6Y-EGFR mutants:GRB2:SOS1 [plasma membrane]

Normal Entity
Disease Entity
Status
Disease
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
Authored
Orlic-Milacic, M  (2011-11-04)
Reviewed
Greulich, H  (2011-11-15)
Savas, S  (2011-11-15)
Created
Orlic-Milacic, M  (2011-03-03)
Cite Us!