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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Wallace, B. G. |
| Description | Author Affiliation: Wallace BG ( Department of Physiology, University of Colorado Health Sciences Center, Denver 80262.) |
| Abstract | Agrin, a protein that mediates nerve-induced acetylcholine receptor (AChR) aggregation at developing neuromuscular junctions, has been shown to cause an increase in phosphorylation of the beta, gamma, and delta subunits of AChRs in cultured myotubes. As a step toward understanding the mechanism of agrin-induced AChR aggregation, we examined the effects of inhibitors of protein kinases on AChR aggregation and phosphorylation in chick myotubes in culture. Staurosporine, an antagonist of both protein serine and tyrosine kinases, blocked agrin-induced AChR aggregation in a dose-dependent manner; 50% inhibition occurred at approximately 2 nM. The extent of inhibition was independent of agrin concentration, suggesting an effect downstream of the interaction of agrin with its receptor. Staurosporine blocked agrin-induced phosphorylation of the AChR beta subunit, which occurs at least in part on tyrosine residues, but did not reduce phosphorylation of the gamma and delta subunits, which occurs on serine/threonine residues. Staurosporine also prevented the agrin- induced decrease in the rate at which AChRs are extracted from intact myotubes by mild detergents. H-7, an antagonist of protein serine kinases, inhibited agrin-induced phosphorylation of the gamma and delta subunits but did not block agrin-induced phosphorylation of the AChR beta subunit, AChR aggregation, or the decrease in AChR extractability. The results provide support for the hypothesis that tyrosine phosphorylation of the beta subunit plays a role in agrin-induced AChR aggregation. |
| ISSN | 00219525 |
| e-ISSN | 15408140 |
| Journal | The Journal of Cell Biology |
| Issue Number | 3 |
| Volume Number | 125 |
| Language | English |
| Publisher | Rockefeller University Press (United States) |
| Publisher Date | 1994-05-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Agrin Pharmacology Alkaloids Receptors, Nicotinic Metabolism Animals Chick Embryo Cytoskeleton Muscles Embryology Phosphoproteins Phosphorylation Phosphotyrosine Protein Kinase C Antagonists & Inhibitors Protein-Tyrosine Kinases Receptor Aggregation Drug Effects Staurosporine Tyrosine Analogs & Derivatives Research Support, U.S. Gov't, P.H.S. Cell Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine |
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