PROTEIN-TYROSINE KINASE-MEDIATED POTENTIATION OF CURRENTS FROM CLONEDNMDA RECEPTORS

Although serine/threonine phosphorylation has been more commonly recog nized as a mechanism to modulate the function of ion channels and rece ptors, tyrosine phosphorylation is under increasing scrutiny. An impor tant subtype of glutamate receptor, the NMDA receptor, is shown to be regulated by insulin via protein tyrosine kinase (PTK). NMDA currents through cloned receptors are potentiated by insulin in a subunit-speci fic manner. The insulin-mediated potentiation of NMDA current is dimin ished by inhibitors of PTKs, At least one exogenous cytosolic PTK, pp6 0(c-src), is also able to potentiate NMDA current. Because later appli cation of PTK inhibitors can reverse the seemingly stable insulin-medi ated potentiation of NMDA current, it appears that tyrosine residues r esponsible For potentiation are continually rephosphorylated by some l ong-term PTK activity that was induced via insulin treatment.