The EGF receptor inhibits the signaling of dopamine D receptor through the phosphorylation of GRK2 on tyrosine residues.

Receptor transactivation or crosstalk are terms referring to instances in which the signaling of a given receptor is regulated by a different class of receptor. The epidermal growth factor (EGF) and the dopaminergic systems in the brain are closely related to schizophrenia with respect to both etiology and treatment. Thus, we investigated the functional interactions between the EGF receptor (EGFR), which belongs to the receptor tyrosine kinase family, and the dopamine D2-like receptors (DR, DR, and DR), which are members of the G protein-coupled receptor (GPCR) family. Among D2-like receptors, the signaling of DR was selectively inhibited by EGFR stimulation. Moreover loss-of-function assays showed that tyrosine-phosphorylated GRK2 mediates this inhibition by acting on the second intracellular loop of DR. Considering that both EGFR and DR are closely related to schizophrenia, this study could provide new molecular insight into the etiology of the disorder.