PMID- 17452444
OWN - NLM
STAT- MEDLINE
DCOM- 20070809
LR  - 20181113
IS  - 0270-7306 (Print)
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Linking)
VI  - 27
IP  - 13
DP  - 2007 Jul
TI  - Analysis of a Shc family adaptor protein, ShcD/Shc4, that associates with 
      muscle-specific kinase.
PG  - 4759-73
AB  - 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.
FAU - Jones, Nina
AU  - Jones N
AD  - Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, 
      Toronto, Ontario, Canada. pawson@mshri.on.ca
FAU - Hardy, W Rod
AU  - Hardy WR
FAU - Friese, Matthew B
AU  - Friese MB
FAU - Jorgensen, Claus
AU  - Jorgensen C
FAU - Smith, Matthew J
AU  - Smith MJ
FAU - Woody, Neil M
AU  - Woody NM
FAU - Burden, Steven J
AU  - Burden SJ
FAU - Pawson, Tony
AU  - Pawson T
LA  - eng
GR  - R01 NS036193/NS/NINDS NIH HHS/United States
GR  - R01 NS036193-10/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20070423
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Agrin)
RN  - 0 (GRB2 Adaptor Protein)
RN  - 0 (Receptors, Cholinergic)
RN  - 0 (SHC4 protein, human)
RN  - 0 (Shc Signaling Adaptor Proteins)
RN  - 0 (Shc4 protein, mouse)
RN  - 42HK56048U (Tyrosine)
RN  - EC 2.7.10.1 (MuSK protein, mouse)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/chemistry/genetics/*metabolism
MH  - Agrin/metabolism
MH  - Amino Acid Sequence
MH  - Animals
MH  - Brain/metabolism
MH  - Cell Line
MH  - GRB2 Adaptor Protein/metabolism
MH  - Gene Expression Profiling
MH  - Humans
MH  - Mice
MH  - Molecular Sequence Data
MH  - Muscle, Skeletal/metabolism
MH  - Neuromuscular Junction/metabolism
MH  - Phosphorylation
MH  - Protein Binding
MH  - Protein Structure, Tertiary
MH  - Protein Transport
MH  - Receptor Protein-Tyrosine Kinases/*metabolism
MH  - Receptors, Cholinergic/metabolism
MH  - Shc Signaling Adaptor Proteins
MH  - Signal Transduction
MH  - Tyrosine/metabolism
PMC - PMC1951494
EDAT- 2007/04/25 09:00
MHDA- 2007/08/10 09:00
PMCR- 2007/11/01
CRDT- 2007/04/25 09:00
PHST- 2007/04/25 09:00 [pubmed]
PHST- 2007/08/10 09:00 [medline]
PHST- 2007/04/25 09:00 [entrez]
PHST- 2007/11/01 00:00 [pmc-release]
AID - MCB.00184-07 [pii]
AID - 0184-07 [pii]
AID - 10.1128/MCB.00184-07 [doi]
PST - ppublish
SO  - Mol Cell Biol. 2007 Jul;27(13):4759-73. doi: 10.1128/MCB.00184-07. Epub 2007 Apr 
      23.