Research article summary (published 8 May 1995):

Phosphorylation of the nicotinic acetylcholine receptor by protein tyrosine kinases.

Full Abstract

Most neurotransmitter receptors examined to date are either regulated by phosphorylation or contain consensus sequences for phosphorylation by protein kinases. The nicotinic acetylcholine 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 tyrosine kinase. Tyrosine phosphorylation of the AChR is correlated with a modulation of the rate of receptor desensitization and is associated with AChR clustering. We showed that agrin, a neuronally derived extracellular matrix protein, induces AChR clustering and tyrosine phosphorylation. In addition, we identified two protein tyrosine kinases, Fyn 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, Fyn and Fyk associate with the AChR. Furthermore, the AChR is phosphorylated in Fyn and Fyk immunoprecipitates. We investigated the molecular basis for the association of the AChR with Fyn and Fyk using fusion proteins derived from the kinases. The AChR bound specifically to the SH2 domain fusion proteins of Fyn and Fyk. The association of the AChR with the SH2 domains is dependent on the state of AChR tyrosine phosphorylation and is mediated by the delta subunit of the receptor. These data provide evidence that the protein tyrosine kinases Fyn and Fyk may act to phosphorylate the AChR in vivo.

Author information

Author/s: Swope, S L (SL); Qu, Z (Z); Huganir, R L (RL);

Affiliation: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

Journal and publication information

Publication Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Review

Journal: Annals of the New York Academy of Sciences (Ann N Y Acad Sci), published in UNITED STATES. (Language: eng)

Reference: 1995-May; vol 757 (issue ) : pp 197-214

Dates: Created 1995/08/15; Completed 1995/08/15; Revised 2006/11/15;

PMID: 7541972, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Agrin - pharmacology Amino Acid Sequence Animals Chickens Mice Molecular Sequence Data Phosphorylation Phosphotyrosine Precipitin Tests Protein Binding - drug effects

Protein Binding - drug effects Protein-Tyrosine Kinases - metabolism Proto-Oncogene Proteins - metabolism Proto-Oncogene Proteins c-fyn Receptors, Nicotinic - metabolism Sequence Alignment Sequence Homology, Amino Acid Synapses - enzymology Torpedo Tyrosine - analogs & derivatives; metabolism

Associated Chemicals: Agrin (0) ; Proto-Oncogene Proteins (0) ; Receptors, Nicotinic (0) ; Phosphotyrosine (21820-51-9) ; Tyrosine (55520-40-6) ; fyk kinase (EC 2.7.1.-) ; Fyn protein, mouse (EC 2.7.1.112) ; Protein-Tyrosine Kinases (EC 2.7.1.112) ; Proto-Oncogene Proteins c-fyn (EC 2.7.1.112)

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