title: Global analysis of muscle-specific kinase signaling by quantitative phosphoproteomics.
abstract: The development of the neuromuscular synapse depends on signaling processes that involve protein phosphorylation as a crucial regulatory event. Muscle-specific kinase (MuSK) is the key signaling molecule at the neuromuscular synapse whose activity is required for the formation of a mature and functional synapse. However, the signaling cascade downstream of MuSK and the regulation of the different components are still poorly understood. In this study we used a quantitative phosphoproteomics approach to study the phosphorylation events and their temporal regulation downstream of MuSK. We identified a total of 10,183 phosphopeptides, of which 203 were significantly up- or down-regulated. Regulated phosphopeptides were classified into four different clusters according to their temporal profiles. Within these clusters we found an overrepresentation of specific protein classes associated with different cellular functions. In particular, we found an enrichment of regulated phosphoproteins involved in posttranscriptional mechanisms and in cytoskeletal organization. These findings provide novel insights into the complex signaling network downstream of MuSK and form the basis for future mechanistic studies.
authors.affiliation: From the ‡Gregor Mendel Institute of Molecular Plant Biology, Dr. Bohr-Gasse 3, 1030 Vienna, Austria; §Institute for Molecular Pathology (IMP), Dr. Bohr-Gasse 7, 1030 Vienna, Austria; ¶Institute of Molecular Biotechnology (IMBA), Dr. Bohr-Gasse 3, 1030 Vienna, Austria;
authors.forename: Gerhard
authors.initials: G
authors.lastname: Dürnberger
authors.affiliation: ‖Center for Brain Research, Medical University of Vienna, Spitalgasse 4, 1090 Vienna, Austria;
authors.forename: Bahar Z
authors.initials: BZ
authors.lastname: Camurdanoglu
authors.affiliation: ‖Center for Brain Research, Medical University of Vienna, Spitalgasse 4, 1090 Vienna, Austria;
authors.forename: Matthias
authors.initials: M
authors.lastname: Tomschik
authors.affiliation: From the ‡Gregor Mendel Institute of Molecular Plant Biology, Dr. Bohr-Gasse 3, 1030 Vienna, Austria; §Institute for Molecular Pathology (IMP), Dr. Bohr-Gasse 7, 1030 Vienna, Austria;
authors.forename: Michael
authors.initials: M
authors.lastname: Schutzbier
authors.affiliation: §Institute for Molecular Pathology (IMP), Dr. Bohr-Gasse 7, 1030 Vienna, Austria; ¶Institute of Molecular Biotechnology (IMBA), Dr. Bohr-Gasse 3, 1030 Vienna, Austria;
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Roitinger
authors.affiliation: §Institute for Molecular Pathology (IMP), Dr. Bohr-Gasse 7, 1030 Vienna, Austria; ¶Institute of Molecular Biotechnology (IMBA), Dr. Bohr-Gasse 3, 1030 Vienna, Austria;
authors.forename: Otto
authors.initials: O
authors.lastname: Hudecz
authors.affiliation: §Institute for Molecular Pathology (IMP), Dr. Bohr-Gasse 7, 1030 Vienna, Austria; ¶Institute of Molecular Biotechnology (IMBA), Dr. Bohr-Gasse 3, 1030 Vienna, Austria;
authors.forename: Karl
authors.initials: K
authors.lastname: Mechtler
authors.affiliation: ‖Center for Brain Research, Medical University of Vienna, Spitalgasse 4, 1090 Vienna, Austria; ‡‡Institute of Immunology, Medical University of Vienna, Lazarettgasse 19, 1090 Vienna, Austria.
authors.forename: Ruth
authors.initials: R
authors.lastname: Herbst
mesh_terms: D018171:Agrin / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D003599:Cytoskeleton / Q000378:metabolism; D005786:Gene Expression Regulation; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism*; D010748:Phosphopeptides / Q000302:isolation & purification* / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D012323:RNA Processing, Post-Transcriptional; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D018171:Agrin; D010748:Phosphopeptides; C511695:MuSK protein, mouse; D020794:Receptor Protein-Tyrosine Kinases