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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
8
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pubmed:dateCreated |
1997-10-14
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pubmed:abstractText |
MuSK is a tyrosine kinase localized to the postsynaptic surface of the neuromuscular junction. We have searched for modulators of MuSK function using a library of human single chain variable region antibodies (scFv) that can be displayed on M13 phage or expressed as soluble protein. A panel of 21 independent MuSK-specific scFv, identified in a screen for binding to MuSK-Fc immunoadhesin, were examined for ability to induce proliferation in a factor dependent cell line (Ba/F3) through a chimeric receptor, MuSK-Mpl. Four of the scFv induced a proliferative response, suggesting an ability to induce dimerization of MuSK. These scFv were also able to induce tyrosine phosphorylation of full-length MuSK and retained this ability when re-engineered to be expressed as authentic (and dimeric) human IgG molecules. Addition of agonist scFv to a cultured myotube cell line induced AChR clustering and tyrosine phosphorylation. These results provide direct evidence that MuSK activation is capable of triggering a key event in neuromuscular junction formation and further demonstrate that large libraries of phage-displayed scFv provide a robust method for generating highly specific agonist agents.
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1087-0156
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
15
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
768-71
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:9255792-Amino Acid Sequence,
pubmed-meshheading:9255792-Animals,
pubmed-meshheading:9255792-Antibodies,
pubmed-meshheading:9255792-Bacteriophage M13,
pubmed-meshheading:9255792-Blotting, Western,
pubmed-meshheading:9255792-Cell Line,
pubmed-meshheading:9255792-Dimerization,
pubmed-meshheading:9255792-Enzyme Activation,
pubmed-meshheading:9255792-Flow Cytometry,
pubmed-meshheading:9255792-Gene Library,
pubmed-meshheading:9255792-Humans,
pubmed-meshheading:9255792-Immunoglobulin Fc Fragments,
pubmed-meshheading:9255792-Immunoglobulin Fragments,
pubmed-meshheading:9255792-Immunoglobulin Variable Region,
pubmed-meshheading:9255792-Mice,
pubmed-meshheading:9255792-Molecular Sequence Data,
pubmed-meshheading:9255792-Muscle Fibers, Skeletal,
pubmed-meshheading:9255792-Neuromuscular Junction,
pubmed-meshheading:9255792-Phosphorylation,
pubmed-meshheading:9255792-Protein Engineering,
pubmed-meshheading:9255792-Receptor Aggregation,
pubmed-meshheading:9255792-Receptor Protein-Tyrosine Kinases,
pubmed-meshheading:9255792-Receptors, Cholinergic,
pubmed-meshheading:9255792-Tyrosine
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pubmed:year |
1997
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pubmed:articleTitle |
Direct demonstration of MuSK involvement in acetylcholine receptor clustering through identification of agonist ScFv.
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pubmed:affiliation |
Department of Molecular Biology, Genentech, Inc., San Francisco, CA 94080, USA.
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pubmed:publicationType |
Journal Article
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