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Signal Transduction Through the Epidermal Growth Factor Receptor Produced by Dr. Steven Pelech Kinexus Bioinformatics Corporation Copyright 2010 EGF EGF EGFR EGFR EGF EGF EGFR EGFR EGF EGFR EGFR EGFR EGF Y869 Y869 Y1016 Y1016 Y1069 EGFR EGFR EGFR Y1092 Y1069 Y1110 Y1110 Y1172 Y1197 Y1092 Y1172 Y1197 EGF Y869 Y869 Y1016 Y1016 Y1069 EGFR EGFR EGFR Y1092 Y1069 Y1110 Y1110 Y1092 Y1172 Y1172 Y1197 Y1197 SH2 SH2 SH2 SH2 SH2 SH2 SH2 Cbl-N PLCg1 Vav2 PTPN11 Ras-GAP Shc1 GrbB2 PTPN6 Cbl SOS EGF Y869 Y869 Y1016 Y1016 Y1069 EGFR EGFR EGFR Y1092 Y1069 Y1110 Y1110 Y1092 Y1172 Y1172 Y1197 Y1197 SH2 SH2 SH2 SH2 SH2 PLCg1 Vav2 PTPN11 Ras-GAP GrbB2 SH2 Shc1 SOS SH2 Cbl-N PTPN6 Cbl EGF Y869 Y869 Y1016 Y1016 Y1069 EGFR EGFR EGFR Y1092 Y1069 Y1110 Y1110 Y1092 Y1172 Y1172 Y1197 Y1197 SH2 SH2 SH2 SH2 SH2 Cbl-N PLCg1 Vav2 PTPN11 Ras-GAP GrbB2 Cbl SH2 Shc1 SOS SH2 PTPN6 EGF Y869 Y869 Y1016 Y1016 Y1069 EGFR EGFR EGFR Y1092 Y1069 Y1110 Y1110 Y1092 Y1172 Y1172 Y1197 Y1197 SH2 SH2 SH2 SH2 SH2 SH2 Cbl-N PLCg1 Vav2 PTPN11 Ras-GAP GrbB2 PTPN6 Cbl SH2 Shc1 SOS EGF Y869 Y869 Y1016 Y1016 Y1069 EGFR EGFR EGFR Y1092 Y1069 Y1110 Y1110 Y1092 Y1172 Y1172 Y1197 Y1197 SH2 SH2 SH2 SH2 SH2 SH2 Cbl-N PLCg1 Vav2 PTPN11 Ras-GAP GrbB2 PTPN6 Cbl SH2 Shc1 SOS EGF Y869 Y869 Y1016 Y1016 Y1069 EGFR EGFR EGFR Y1092 Y1069 Y1110 Y1110 Y1092 Y1172 Y1172 Y1197 Y1197 SH2 SH2 SH2 SH2 SH2 SH2 Cbl-N PLCg1 Vav2 PTPN11 Ras-GAP GrbB2 PTPN6 Cbl SH2 Shc1 SOS EGF Y869 Y869 Y1016 Y1016 Y1069 EGFR EGFR EGFR Y1092 Y1069 Y1110 Y1110 Y1092 Y1172 Y1172 Y1197 Y1197 SH2 SH2 SH2 SH2 SH2 SH2 SH2 Cbl-N PLCg1 Vav2 PTPN11 Ras-GAP Shc1 GrbB2 PTPN6 Cbl SOS EGF Y869 Y869 Y1016 Y1016 Y1069 EGFR EGFR EGFR Y1092 Y1069 Y1110 Y1110 Y1172 Y1172 Y1197 Y1197 SH2 Y771 Y775 Y783 Y1253 PLCg1 Y1092 SH2 Y142 Y159 Y172 Vav2 SH2 Y542 S576 Y580 S591 PTPN11 SH2 Ras-GAP SH2 Y349 Y350 Y427 Shc1 SH2 Y209 GrbB2 SH2 Y654 Y350 PTPN6 SOS Cbl-N Y371 Y552 Y674 Y700 Y731 Y774 Cbl EGF Y869 Y869 Y1016 Y1016 Y1069 EGFR EGFR EGFR Y1092 Y1069 Y1110 Y1110 Y1172 Y1197 SH2 Y771 Y775 Y783 Y1253 PLCg1 SH2 Y142 Y159 Y172 Vav2 SH2 Y542 S576 Y580 S591 PTPN11 SH2 Ras-GAP Y1092 Y1172 Y1197 SH2 Y349 Y350 Y427 Shc1 SH2 Y209 GrbB2 SH2 Y654 Y350 PTPN6 SOS Cbl-N Y371 Y552 Y674 Y700 Y731 Y774 Cbl EGF Y869 Y1016 Y1069 EGFR EGFR EGFR Y1092 Y1110 Y1172 Y1197 PLCg1 Vav2 PTPN11 Ras-GAP Shc1 GrbB2 SOS PTPN6 Cbl EGF Y869 T678 Y1016 EGFR EGFR EGFR Y1069 Y1092 S1070 PKCa PKCb S1071 Y1110 Y1172 Y1197 PIP2 DAG + IP3 PLCg1 Ca2+ CaMK2 CaMK2 CALCISOMES EGF T678 Y869 T693 Y1016 EGFR EGFR EGFR Y1069 Y1092 S1070 Y1110 S1071 Y1172 Y1197 Vav2 T423 Rac PAKa MEKK? S189 T193 T179 Y181 MEK3 p38a EGF T678 Y869 T693 S695 ? PKCa Y1016 PKCb S1026 Y1092 S1070 Y1110 S1071 S1190 S338 S339 Y340 Y341 S497 S499 Raf1 Y1069 EGFR EGFR EGFR PTPN11 Ras-GAP Y1172 Src Y1197 Shc1 GrbB2 SOS PAKa Ras S218 S222 T184 Y186 Mek1 Erk2 EGF T678 Y869 T693 S695 PKCa PKCb Y1016 EGFR Y1069 S1026 Y1092 S1070 Y1110 S1071 S1190 PTPN11 EGFR Y1172 Src Y1197 PTPN6 EGF T678 Y869 T693 S695 PKCa PKCb Y1016 EGFR EGFR Y1069 S1026 Y1092 S1070 Y1110 S1071 Y1172 S1190 Y813 JAK2 Y1197 Y542 S576 Y580 S591 Y536 Y654 PTPN6 PTPN11 SH2 Y701 SH2 Y705 S727 Stat1 Stat3 Src EGF T678 Y869 T693 S695 Y1016 EGFR EGFR Y1069 S1026 Y1092 S1070 Y1110 S1071 S1190 Y1172 Src Y1197 Cbl EGF T678 Y869 T693 S695 Y1016 EGFR EGFR Y1069 S1026 Y1092 S1070 Y1110 S1071 S1190 Y1172 Src Y1197 Ubiquitination + Degradation by 20S Proteosome Cbl-N Y371 Y552 Y674 Y700 Y731 Y774 Cbl EGF Receptor ErbB1 Betacellulin EGF Epiregulin HB-EGF P01133 O14944 Q99075 TGFa P01135 P35070 Amphiregulin EGFR P15514 P00533 Y1197 Y1110 Y1172 Y1069 Y869 Y1092 Y1016 EGFR P00533 Y371 Y552 Y674 Y700 Y731 Y774 Y1016 Y1172 Y1069 Y1016 SH2 Y1092 Y209 Y1092 Y1197 Y1092 Y1092 Y1197 Y1172 SH2 SH2 Y771 Y775 Y1253 Y783 SH2 Y350 Y654 SH2 Y1197 Y1016 SH2 P22681 GrbB2 Y1016 Y1092 Y1197 SH2 Cbl Y1016 SH2 Y142 Y159 Y172 SH2 Vav2 Y349 Y350 Y427 Y542 Y580 P52735 Shc1 P29353 P62993 PLCg1 P19174 Ras-GAP PLCg1 P19174 PTPN6 P29350 PTPN11 Q06124 P20936