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This is Melanie Cobb,
and I'll be talking to you about
the ERK1/2 MAP Kinase Pathway.
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The pathway is activated by
many extracellular ligands
and a number of intracellular cues.
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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.
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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.
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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.
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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.
