BIOL 238 |
| p38a is a Mitogen-Activated Protein (MAP) Kinase that controls the production of inflammatory cytokines and growth factors in response to extracellular stress signals. High p38a concentrations, causing the overproduction of inflammatory cytokines, such as interleukin 6, are a main characteristic of many inflammatory diseases including rheumatoid arthritis. MAP kinases JNK, ERK, and p38 are similar in structure and exhibit little specificity for short peptide substrates. Thus, assays that distinguish among the activity of MAP kinases have required full-length protein substrates. The specificity of MAP kinases appears to result from allosteric docking sites that regulate the efficiency and selectivity of the enzyme. We have shown that by adding a properly spaced docking peptide to a short substrate peptide we can increase KM of the substrate 10 fold; however, increases in kcat/KM are more modest. Most important, in vitro assays have shown our designed substrates to be selectively phosphorylated by p38a and not by ERK1. |
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Enzymes
4:30 PM-6:30 PM, Wednesday, 13 September 2006 Moscone Center -- Hall D, Poster
Sci-Mix
Division of Biological Chemistry |