Protein phosphorylation is an important mechanism modulating the function of NMDA receptors (NMDARs). SRC-family kinases that associate with EPHB are important for the phosphorylation of ionotropic glutamate receptor, NR2B (NMDAR2B, GRIN2B) Tyrosines 1252, 1336, and 1474 (1252, 1336, and 1472 in mouse) on NR2B are phosphorylated by FYN/SRC bound to EPHB2, thereby enhancing NMDA-dependent calcium influx upon glutamate stimulation (Takasu et al. 2002, Dalva et al. 2000). Tyrosine phosphorylation of NMDAR2B also regulates the surface expression of NMDARs. EPHB mediated phosphorylation of NMDARs can also increase the surface retention of NMDAR2B-containing NMDARs by preventing clathrin-dependent endocytosis. Phosphorylation at tyrosine 1474 (mouse Y1472) of NMDAR2B blocks binding of the mu2 subunit of clathrin adaptor protein 2 (AP2) complex thus preventing clathrin-dependent endocytosis (Chen & Roche 2007).