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Details on Person The Src homology 2 (SH2) domain of the phosphatidylinositol ...

Class:IdSummation:188530
_displayNameThe Src homology 2 (SH2) domain of the phosphatidylinositol ...
_timestamp2017-12-01 15:14:01
created[InstanceEdit:188528] Jassal, B, 2006-10-17 11:04:33
literatureReference[LiteratureReference:179899] A novel positive feedback loop mediated by the docking protein Gab1 and phosphatidylinositol 3-kinase in epidermal growth factor receptor signaling
[LiteratureReference:179884] Unique phosphorylation mechanism of Gab1 using PI 3-kinase as an adaptor protein
[LiteratureReference:2327862] A frequent kinase domain mutation that changes the interaction between PI3Kalpha and the membrane
[LiteratureReference:2327861] Dynamics of the phosphoinositide 3-kinase p110? interaction with p85? and membranes reveals aspects of regulation distinct from p110?
modified[InstanceEdit:1568624] Orlic-Milacic, Marija, 2011-09-06
[InstanceEdit:9031667] Orlic-Milacic, Marija, 2017-12-01
textThe Src homology 2 (SH2) domain of the phosphatidylinositol 3-kinase (PIK3) regulatory subunit (PIK3R1, i.e. PI3Kp85) binds to GAB1 in a phosphorylation-independent manner. GAB1 serves as a docking protein which recruits a number of downstream signalling proteins. PIK3R1 can bind to either GAB1 or phosphorylated GAB1(Rodrigues et al. 2000, Onishi-Haraikawa et al. 2001). In unstimulated cells, PI3K class IA exists as an inactive heterodimer of a p85 regulatory subunit (encoded by PIK3R1, PIK3R2 or PIK3R3) and a p110 catalytic subunit (encoded by PIK3CA, PIK3CB or PIK3CD). Binding of the iSH2 domain of the p85 regulatory subunit to the ABD and C2 domains of the p110 catalytic subunit both stabilizes p110 and inhibits its catalytic activity. This inhibition is relieved when the SH2 domains of p85 bind phosphorylated tyrosines on activated RTKs or their adaptor proteins. Binding to membrane-associated receptors brings activated PI3K in proximity to its membrane-localized substrate, PIP2 (Mandelker et al. 2009, Burke et al. 2011).
(summation)[Reaction:177927] PI3K binds to EGF:EGFR:GRB2:GAB1 [Homo sapiens]
[Reaction:5654591] Activated FGFR1:p-FRS2:GRB2:GAB1:PI3KR1 binds PIK3CA [Homo sapiens]
[Reaction:5654596] Activated FGFR1:p-FRS2:p-PPTN11:GRB2:GAB1:PIK3R1 binds PIK3CA [Homo sapiens]
[Reaction:5654614] Activated FGFR2:p-FRS2:GRB2:GAB1:PI3KR1 binds PIK3CA [Homo sapiens]
[Reaction:5654622] Activated FGFR2:p-FRS2:p-PPTN11:GRB2:GAB1:PIK3R1 binds PIK3CA [Homo sapiens]
[Reaction:5654640] Activated FGFR3:p-FRS2:GRB2:GAB1:PI3KR1 binds PIK3CA [Homo sapiens]
[Reaction:5654643] Activated FGFR3:p-FRS2:p-PPTN11:GRB2:GAB1:PIK3R1 binds PIK3CA [Homo sapiens]
[Reaction:5654662] Activated FGFR4:p-FRS2:GRB2:GAB1:PI3KR1 binds PIK3CA [Homo sapiens]
[Reaction:5654669] Activated FGFR4:p-FRS2:p-PPTN11:GRB2:GAB1:PIK3R1binds PIK3CA [Homo sapiens]
[Reaction:9846385] GOCAM PI3K binds to EGF:EGFR:GRB2:GAB1 [Homo sapiens]
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