Docking protein 1 (DOK 1), 2, 4, 5, and 6 adaptor proteins all interact with RET at phosphorylated tyrosine-1062 (Y1062) (Grimm et al. 2001, Crowder et al. 2004, Kurotsuchi et al. 2010).
DOKs are adaptor proteins that can inhibit mitogen-activated protein kinase (MAPK) signaling, cell proliferation, and cellular transformation. DOK1 and 2 may exert their inhibitory effects by recruiting Ras GTPase-activating protein 1 (RASA1, RasGAP), which is a negative regulator of Ras signaling, but DOK2 can attenuate EGF receptor-induced MAP kinase activation without RASA1. DOK3 negatively regulates signaling by recruiting INPP5D and CSK (Grimm et al. 2001).
RET promotes neurite outgrowth of the rat pheochromocytoma cell line PC12 via Y1062. RET-DOK4/5 fusion proteins induced ligand-dependent axonal outgrowth of PC12 cells, while RET-DOK2 fusions did not. DOK4/5 do not associate with RASA1 or NCK, and enhance RET-dependent activation of MAPK (Grimm et al. 2001).