Reaction: Trans-autophosphorylation of ERBB4 homodimers
- in pathway: Signaling by ERBB4
Homodimers of ERBB4 CYT 1 isoforms trans autophosphorylate on six tyrosine residues (three on each monomer) that serve as docking sites for SHC1 (tyrosines Y1188 and 1242 in the isoform ERBB4 JM-A CYT1; tyrosines Y1178 and Y1232 in the isoform ERBB4 JM-B CYT1) and the p85 subunit of PI3K (tyrosine Y1056 in the isoform ERBB4 JM-A CYT1; tyrosine Y1046 in the isoform ERBB4 JM-B CYT1), while ERBB4 CYT2 isoform homodimer trans-autophosphorylates on four SHC1 binding tyrosines (two on each monomer - tyrosines Y1172 and Y1226) (Cohen et al. 1996, Kaushansky et al. 2008).
NRG1-mediated activation of ERBB4 signaling negatively regulates, via an unknown mechanism, phosphorylation of NMDA receptors by SRC. ERBB4 signaling is hyperactivated in schizophrenia, while SRC-mediated phosphorylation of NMDA receptors (NMDARs) is reduced in schizophrenia. (Pitcher et al. 2011, Banerjee et al. 2015).
NRG1-mediated activation of ERBB4 signaling negatively regulates, via an unknown mechanism, phosphorylation of NMDA receptors by SRC. ERBB4 signaling is hyperactivated in schizophrenia, while SRC-mediated phosphorylation of NMDA receptors (NMDARs) is reduced in schizophrenia. (Pitcher et al. 2011, Banerjee et al. 2015).
Reaction - small molecule participants:
ADP [cytosol]
ATP [cytosol]
Reactome.org reaction link: R-HSA-1250315
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Reaction input - small molecules:
ATP(4-)
Reaction output - small molecules:
ADP(3-)
Reactome.org link: R-HSA-1250315