School of Biomedical Sciences,
Faculty of Medicine and Health Sciences,
Queens Medical Centre, Nottingham NG7 2UH, UK.

 
   Mitogen-Activated Protein Kinases
 

 
Although several mammalian MAPK cascades are now known to exist, our work has focussed on the regulation of ERKs and their upstream activators, MEKs and Raf kinases. Insofar as signal transmission involves successive phosphorylation events, the cascade can be considered linear. However, signal transmission is modulated by the interaction of numerous other pathway components, such as scaffold proteins and other kinases, the latter targeting regulatory phosphorylation sites. In addition to studying these modulatory phosphorylation events we have also tried to address the question of why multiple ERK, MEK and Raf isoforms are highly conserved yet appear to be redundant.

References

Coles, L.C. and Shaw, P.E. (2002).  PAK1 primes MEK1 for phosphorylation by Raf-1 kinase during cross-cascade activation of the ERK pathway. Oncogene 21, 2236-2244.

Dhillon, A.S., Steen, H., Shaw, P.E., Mischak, H. and Kölch W.  (2002).  The cAMP Dependent Kinase Regulates the Raf-1 Kinase Mainly by Phosphorylation of Serine 259. Mol. Cell. Biol. 22, 3237-3246

Brummer, T., Shaw, P.E., Reth, M. and Misawa, Y. (2002) Inducible gene deletion reveals different roles for B-Raf and Raf-1 in B-cell antigen receptor signalling EMBO J. 21, 5611-5622

Dhillon, A.S., Meikle, S., Grindlay, J., Kaiser, C., Steen, H., Shaw, P.E., Mischak, H. Eychene, A. and Kölch W. (2003). A Raf-1 mutant that dissociates MEK/ERK Activation from Malignant Transformation and Differentiation but not Differentiation. Mol. Cell. Biol. 23, 1983-1993


Back Home



last modified 12.8.03