This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Jones, N.
Right arrow Articles by Pawson, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jones, N.
Right arrow Articles by Pawson, T.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, July 2007, p. 4759-4773, Vol. 27, No. 13
0270-7306/07/$08.00+0     doi:10.1128/MCB.00184-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Analysis of a Shc Family Adaptor Protein, ShcD/Shc4, That Associates with Muscle-Specific Kinase{triangledown}

Nina Jones,1* W. Rod Hardy,1,2 Matthew B. Friese,3 Claus Jorgensen,1 Matthew J. Smith,1,2 Neil M. Woody,1 Steven J. Burden,3 and Tony Pawson1,2*

Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario, Canada M5G 1X5,1 Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, Canada,2 Molecular Neurobiology Program, Skirball Institute for Biomolecular Medicine, New York University Medical School, New York, New York3

Received 31 January 2007/ Returned for modification 12 March 2007/ Accepted 13 April 2007

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.

* Corresponding author. Mailing address for Tony Pawson: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario, Canada M5G 1X5. Phone: (416) 586-8262. Fax: (416) 586-8869. E-mail: pawson{at}mshri.on.ca. Present address for Nina Jones: Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada N1G 2W1. Phone: (519) 824-4120, ext. 53643. Fax: (519) 837-1802. E-mail: jonesmcb{at}uoguelph.ca

{triangledown} Published ahead of print on 23 April 2007.

Molecular and Cellular Biology, July 2007, p. 4759-4773, Vol. 27, No. 13
0270-7306/07/$08.00+0     doi:10.1128/MCB.00184-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Savino, M. T., Ortensi, B., Ferro, M., Ulivieri, C., Fanigliulo, D., Paccagnini, E., Lazzi, S., Osti, D., Pelicci, G., Baldari, C. T. (2009). Rai Acts as a Negative Regulator of Autoimmunity by Inhibiting Antigen Receptor Signaling and Lymphocyte Activation. J. Immunol. 182: 301-308 [Abstract] [Full Text]  
  • Zhu, D., Yang, Z., Luo, Z., Luo, S., Xiong, W. C., Mei, L. (2008). Muscle-Specific Receptor Tyrosine Kinase Endocytosis in Acetylcholine Receptor Clustering in Response to Agrin. J. Neurosci. 28: 1688-1696 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»