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Activation of muscle-specific receptor tyrosine kinase and binding to dystroglycan are regulated by alternative mRNA splicing of agrin
- Source :
- The Journal of biological chemistry, 281 (2006): 36835–36845., info:cnr-pdr/source/autori:Scotton P., Bleckmann D., Stebler M., Sciandra F., Brancaccio A., Meier T., Stetefeld J., Ruegg M.A./titolo:Activation of muscle-specific receptor tyrosine kinase and binding to dystroglycan are regulated by alternative mRNA splicing of agrin/doi:/rivista:The Journal of biological chemistry (Print)/anno:2006/pagina_da:36835/pagina_a:36845/intervallo_pagine:36835–36845/volume:281
- Publication Year :
- 2006
-
Abstract
- Agrin induces the aggregation of postsynaptic proteins at the neuromuscular junction (NMJ). This activity requires the receptor-tyrosine kinase MuSK. Agrin isoforms differ in short amino acid stretches at two sites, called A and B, that are localized in the two most C-terminal laminin G (LG) domains. Importantly, agrin isoforms greatly differ in their activities of inducing MuSK phosphorylation and of binding to alpha-dystroglycan. By using site-directed mutagenesis, we characterized the amino acids important for these activities of agrin. We find that the conserved tripeptide asparagineglutamate- isoleucine in the eight-amino acid long insert at the B-site is necessary and sufficient for full MuSK phosphorylation activity. However, even if all eight amino acids were replaced by alanines, this agrin mutant still has significantly higher MuSK phosphorylation activity than the splice version lacking any insert. We also show that binding to alpha-dystroglycan requires at least two LG domains and that amino acid inserts at the A and the B splice sites negatively affect binding.
- Subjects :
- Gene isoform
animal structures
Molecular Sequence Data
Biochemistry
Neuromuscular junction
Mice
Laminin
medicine
Dystroglycan
Animals
Humans
Agrin
Amino Acid Sequence
RNA, Messenger
Dystroglycans
Molecular Biology
chemistry.chemical_classification
Binding Sites
biology
Sequence Homology, Amino Acid
Kinase
Muscles
Receptor Protein-Tyrosine Kinases
Cell Biology
Amino acid
Alternative Splicing
medicine.anatomical_structure
nervous system
chemistry
biology.protein
Phosphorylation
Chickens
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 281
- Issue :
- 48
- Database :
- OpenAIRE
- Journal :
- The Journal of biological chemistry
- Accession number :
- edsair.doi.dedup.....4412a57b40497c0465071b87dc54b53e