Phosphorylation of the nicotinic XXXX receptor by protein @entity669 kinases.

@entity7984 @entity12571 @entity669 @entity934
Most neurotransmitter receptors examined to date are either regulated by phosphorylation or contain consensus sequences for phosphorylation by protein kinases. The nicotinic @entity934 receptor (AChR), which mediates depolarization at the neuromuscular junction, has served as a model for the study of the structure, function, and regulation of ligand-gated ion channels. The AChR is phosphorylated by protein kinase A, protein kinase C, and an unidentified protein @entity669 kinase. @entity669 phosphorylation of the AChR is correlated with a modulation of the rate of receptor desensitization and is associated with AChR clustering. We showed that @entity12571 , a neuronally derived extracellular matrix protein, induces AChR clustering and @entity669 phosphorylation. In addition, we identified two protein @entity669 kinases, @entity7984 and Fyk, that appear to be involved in the regulation of synaptic transmission at the neuromuscular junction by phosphorylating the AChR. The two kinases are highly expressed in Torpedo electric organ, a tissue enriched in synaptic components including the AChR. As demonstrated by coimmunoprecipitation, @entity7984 and Fyk associate with the AChR. Furthermore, the AChR is phosphorylated in @entity7984 and Fyk immunoprecipitates. We investigated the molecular basis for the association of the AChR with @entity7984 and Fyk using fusion proteins derived from the kinases. The AChR bound specifically to the SH2 domain fusion proteins of @entity7984 and Fyk. The association of the AChR with the SH2 domains is dependent on the state of AChR @entity669 phosphorylation and is mediated by the delta subunit of the receptor. These data provide evidence that the protein @entity669 kinases @entity7984 and Fyk may act to phosphorylate the AChR in vivo.
