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
plasma membrane, cytosol, extracellular region
ReviewStatus
5/5
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Conversion of PIP2 to PIP3 by PI3K bound to ligand-responsive p-6Y-EGFR mutants
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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 N771_H773dup mutant (Xu et al. 2007); EGFR K739_I744dup mutant (Xu et al. 2007); EGFR A767_V769dup mutant (Xu et al. 2007); EGFR E746_A750del;T790M double mutant (Shimamura et al. 2005).
Literature References
PubMed ID Title Journal Year
17177598 Epidermal growth factor receptor activation in glioblastoma through novel missense mutations in the extracellular domain

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

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

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

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

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

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

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

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, Shapiro, GI, Engelman, JA

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

phosphatidylinositol-4,5-bisphosphate 3-kinase activity of Ligand-responsive p-6Y-EGFR mutants:GRB2:GAB1:PI3K [plasma membrane]

Physical Entity
Ligand-responsive p-6Y-EGFR mutants:GRB2:GAB1:PI3K [plasma membrane] (Homo sapiens)
Activity
phosphatidylinositol-4,5-bisphosphate 3-kinase activity (GO:0046934)
Normal reaction
PI3K converts phosphatidylinositol-4,5-bisphosphate (PIP2) to phosphatidylinositol-3,4,5-trisphosphate (PIP3) (Homo sapiens)
Functional status

Gain of function of Ligand-responsive p-6Y-EGFR mutants:GRB2:GAB1:PI3K [plasma membrane]

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