TY - JOUR T1 - Tyrosine Phosphorylation of Nicotinic Acetylcholine Receptor Mediates Grb2 Binding JF - The Journal of Neuroscience JO - J. Neurosci. SP - 5038 LP - 5045 DO - 10.1523/JNEUROSCI.17-13-05038.1997 VL - 17 IS - 13 AU - Marcie Colledge AU - Stanley C. Froehner Y1 - 1997/07/01 UR - http://www.jneurosci.org/content/17/13/5038.abstract N2 - Tyrosine phosphorylation of the nicotinic acetylcholine receptor (AChR) is associated with an altered rate of receptor desensitization and also may play a role in agrin-induced receptor clustering. We have demonstrated a previously unsuspected interaction betweenTorpedo AChR and the adaptor protein Grb2. The binding is mediated by the Src homology 2 (SH2) domain of Grb2 and the tyrosine-phosphorylated δ subunit of the AChR. Dephosphorylation of the δ subunit abolishes Grb2 binding. A cytoplasmic domain of the δ subunit contains a binding motif (pYXNX) for the SH2 domain of Grb2. Indeed, a phosphopeptide corresponding to this region of the δ subunit binds to Grb2 SH2 fusion proteins with relatively high affinity, whereas a peptide lacking phosphorylation on tyrosine exhibits no binding. Grb2 is colocalized with the AChR on the innervated face of Torpedo electrocytes. Furthermore, Grb2 specifically copurifies with AChR solubilized from postsynaptic membranes. These data suggest a novel role for tyrosine phosphorylation of the AChR in the initiation of a Grb2-mediated signaling cascade at the postsynaptic membrane. ER -