Conversion of PIP2 to PIP3 by PI3K bound to ligand-responsive p-6Y-EGFR mutants

Stable Identifier
R-HSA-1226014
Type
Reaction [transition]
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
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

The kinase activity of PI3K mediates the phosphorylation of PIP2 to form PIP3. It is assumed that EGFR cancer mutants induce PI3K/AKT signaling in a manner similar to wild-type EGFR. Phosphorylation of AKT on serine residue S473, and therby activation of PI3K/AKT signaling cascade, has been directly demonstrated in cells expressing the following EGFR cancer mutants: EGFR L858R mutant (Sordella et al. 2004, Paez et al. 2004, Greulich et al. 2005, Shimamura et al. 2005); EGFR G719S mutant (Greulich et al. 2005); EGFR E746_A750del mutant (Sordella et al. 2004, Shimamura et al. 2005); EGFR L747_P753insS mutant (Sordella et al. 2004); EGFR L747_A750delinsP mutant (Greulich et al. 2005); EGFR L861Q mutant (Lee et al. 2006); EGFR D770_N771insNPG mutant (Greulich et al. 2005, Xu et al. 2007); EGFR D770_N771insNPH mutant (Xu et al. 2007); EGFR V738_K739insKIPVAI mutant (Xu et al. 2007); EGFR M766_A767insASV mutant (Xu et al. 2007); 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

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
17177598 Epidermal growth factor receptor activation in glioblastoma through novel missense mutations in the extracellular domain

Lee, JC, Vivanco, I, Beroukhim, R, Huang, JHY, Feng, WL, DeBiasi, RM, Yoshimoto, K, King, JC, Nghiemphu, P, Yuza, Y, Xu, Q, Greulich, H, Thomas, RK, Paez, JG, Peck, TC, Linhart, DJ, Glatt, KA, Getz, G, Onofrio, R, Ziaugra, L, Levine, RL, Gabriel, S, Kawaguchi, T, O'Neill, K, Khan, H, Liau, LM, Nelson, SF, Rao, PN, Mischel, P, Pieper, RO, Cloughesy, T, Leahy, DJ, Sellers, WR, Sawyers, CL, Meyerson, M, Mellinghoff, IK

PLoS Med 2006
16187797 Oncogenic transformation by inhibitor-sensitive and -resistant EGFR mutants

Greulich, H, Chen, TH, Feng, WL, Jänne, PA, Alvarez, JV, Zappaterra, M, Bulmer, SE, Frank, DA, Hahn, WC, Sellers, WR, Meyerson, M

PLoS Med 2005
15284455 Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways

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

Science 2004
17712310 Sensitivity of epidermal growth factor receptor and ErbB2 exon 20 insertion mutants to Hsp90 inhibition

Xu, W, Soga, S, Beebe, K, Lee, MJ, Kim, YS, Trepel, J, Neckers, LM

Br J Cancer 2007
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
phosphatidylinositol-4,5-bisphosphate 3-kinase activity of Ligand-responsive p-6Y-EGFR mutants:GRB2:GAB1:PI3K [plasma membrane]
Physical Entity
Activity
Normal reaction
Disease
Name Identifier Synonyms
cancer 162 malignant tumor, malignant neoplasm, primary cancer
Authored
Reviewed
Created
Cite Us!