Analysis of a Shc Family Adaptor Protein, ShcD/Shc4, That Associates with Muscle-Specific Kinase
- 1 July 2007
- journal article
- research article
- Published by Informa UK Limited in Molecular and Cellular Biology
- Vol. 27 (13), 4759-4773
- https://doi.org/10.1128/mcb.00184-07
Abstract
Shc family proteins serve as phosphotyrosine adaptor molecules in various receptor-mediated signaling pathways. In mammals, three distinct Shc genes have been described that encode proteins characterized by two phosphotyrosine-interaction modules, an amino-terminal phosphotyrosine binding (PTB) domain and a carboxy-terminal Src homology 2 domain. Here, we report the analysis of an uncharacterized fourth Shc family protein, ShcD/Shc4, that is expressed in adult brain and skeletal muscle. Consistent with this expression pattern, we find that ShcD can associate via its PTB domain with the phosphorylated muscle-specific kinase (MuSK) receptor tyrosine kinase and undergo tyrosine phosphorylation downstream of activated MuSK. Interestingly, additional sites of tyrosine phosphorylation, including a novel Grb2 binding site, are present on ShcD that are not found in other Shc family proteins. Activation of MuSK upon agrin binding at the neuromuscular junction (NMJ) induces clustering and tyrosine phosphorylation of acetylcholine receptors (AChRs) required for synaptic transmission. ShcD is coexpressed with MuSK in the postsynaptic region of the NMJ, and in cultured myotubes stimulated with agrin, expression of ShcD appears to be important for early tyrosine phosphorylation of the AChR. Thus, we have characterized a new member of the Shc family of docking proteins, which may mediate a specific aspect of signaling downstream of the MuSK receptor.Keywords
This publication has 59 references indexed in Scilit:
- RaLP, a New Member of the Src Homology and Collagen Family, Regulates Cell Migration and Tumor Growth of Metastatic MelanomasCancer Research, 2007
- Screening for PTB Domain Binding Partners and Ligand Specificity Using Proteome-Derived NPXY Peptide ArraysMolecular and Cellular Biology, 2006
- A Single Pulse of Agrin Triggers a Pathway That Acts To Cluster Acetylcholine ReceptorsMolecular and Cellular Biology, 2004
- Postsynaptic requirement for Abl kinases in assembly of the neuromuscular junctionNature Neuroscience, 2003
- The Neuron-Specific Rai (ShcC) Adaptor Protein Inhibits Apoptosis by Coupling Ret to the Phosphatidylinositol 3-Kinase/Akt Signaling PathwayMolecular and Cellular Biology, 2002
- T-coffee: a novel method for fast and accurate multiple sequence alignment 1 1Edited by J. ThorntonJournal of Molecular Biology, 2000
- Neuregulin‐Increased Expression of Acetylcholine Receptorε‐Subunit Gene Requires ErbB Interaction with ShcJournal of Neurochemistry, 1999
- Functional Interaction of Src Family Kinases with the Acetylcholine Receptor in C2 MyotubesJournal of Biological Chemistry, 1996
- Defective Neuromuscular Synaptogenesis in Agrin-Deficient Mutant MiceCell, 1996
- The Receptor Tyrosine Kinase MuSK Is Required for Neuromuscular Junction Formation In VivoCell, 1996