The ERK1/2 MAPK cascade

Published on December 2, 2014   29 min

A selection of talks on Biochemistry

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This is Melanie Cobb, and I'll be talking to you about the ERK1/2 MAP Kinase Pathway.
The pathway is activated by many extracellular ligands and a number of intracellular cues.
The form of the MAPK cascade is conserved across eukaryotes initially identified in yeast and often thought of as linear, consisting of three kinases activated in series. Often there are upstream kinases that enhance or regulate activation of this core.
In metazoans, the organization of these cascades is pretty well conserved. In many cases cascades have protein kinases that are substrates. So for example, ERK has at least 7 or 8 protein kinase substrates, including MNKs, MSKs, and the first-identified RSK protein kinases.
It's important to remember that this pathway fits in a densely packed network of interacting molecules that will influence pathway output. Context is essential in understanding what this pathway will do. It doesn't act in a vacuum.
ERK2 is an essential gene within prominent roles and disease processes. ERK 1 and 2 are about 83% identical with many of the differences in the termini or insert regions and are thought to have largely overlapping functions, although issues about this question still remain. Mutations in receptor KRas and BRaf are widespread in cancer. There are mutations in MEK and also ERK2 that have been identified, but they're much less commonly occurring. Mutations or deletions at several genes in the Ras/ERK pathway also cause developmental syndromes that account for a fraction of birth defects.