GRB2, 188.8.131.52, MEK2(MAP2K2), EGFR, PDK (PDPK1), Dopamine D2 receptor, HB-EGF, MEK1(MAP2K1), PI3K cat class IA, ADAM12, PtdIns(3,4,5)P3, Shc, PI3K reg class IA, AKT, ERK2 (MAPK1), Dopamine extracellular region, G-protein alpha-i family, SOS, ERK1 (MAPK3), c-Src, c-Raf-1, G-protein beta/gamma, H-Ras, PtdIns(4,5)P2
Dopamine D2 receptor transactivation of EGFR
Dopamine is a major transmitter and neuromodulator in the CNS. This transmitter mediates its signaling through GPCRs of which the Dopamine receptor D2 ( Dopamine D2 receptor ) class of dopamine receptors is a common target for most antipsychotics. Dopamine can also transactivate members of receptor tyrosine kinases family, such Epidermal growth factor receptor ( EGFR ).
Dopamine D2 receptor transactivation of EGFR implicates V-src sarcoma viral oncogene homolog ( c-Src ) via at least two mechanisms: direct phosphorylation of EGFR and/or phosphorylation of some matrix metalloproteinases (e.g. ADAM metallopeptidase domain 12 ( ADAM12 )) , , .
EGFR leads to distinct downstream signaling events, one of which is mediated by transactivation of EGFR via Mitogen-activated protein kinases 3 and 1 ( ERK1(MAPK3), ERK2(MAPK1) ) pathways , , .
After EGFR phosphorylation, the receptor recruits adaptor proteins Src homology 2 domain containing transforming protein ( Shc ) and Growth factor receptor bound 2 ( Grb2 ). In addition, Shc may be activated via Phosphoinositide-3-kinase ( PI3K ). Activated Shc and Grb2 recruit Son of sevenless proteins ( SOS ) to the small GTPase v-Ha-ras Harvey rat sarcoma viral oncogene homolog ( H-Ras ). This results in rapid activation of H-Ras and subsequent activation of V-raf-1 murine leukemia viral oncogene homolog 1 ( c-Raf-1 )/ Mitogen-activated protein kinase kinase 1 and 2 ( MEK1(MAP2K1) and MEK2(MAP2K2) )/ ERK1(MAPK3), ERK2(MAPK1) cascade , .
In addition, EGFR may activate Phosphoinositide-3-kinase ( PI3K )/ V-akt murine thymoma viral oncogene homolog ( AKT(PKB) ) and thus, regulate cell survival during oxidative stress .