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Printable Handouts
Navigable Slide Index
- Introduction
- The ERK1/2 MAPK cascade
- MAPK cascade paradigm
- MAPK multi-cascade paradigm
- ERK1/2 in the big picture
- ERK1/2 in disease and development
- Properties of MAPK cascades
- Ras activates the ERK1/2 MAPK cascade
- Threshold in ERK1/2 activation
- Inactivation of ERK1/2
- Structure of ERK2
- Specialized kinase motifs
- MEK1 motifs
- Enzymatic specificity of MEKs
- Off-target effects of common MEK inhibitors
- ERK2 interactions
- MAPK insert
- Raf oligomerization
- Raf, KSR and MAP3K complexity
- Resistance to B-Raf inhibitors
- B-Raf inhibitors as cancer chemotherapeutics
- Raf signaling and the Hippo pathway
- Multiple MAP3Ks can activate ERK1/2
- Kinetics and ERK1/2 output
- Growth factor mechanisms
- Feedback phosphorylation of SOS
- Feedback Phosphorylation of B-Raf
- Protein phosphatases inactivate ERK1/2
- Dual-specificity MAPK phosphatases
- DUSP/MKP regulatory circuits
- ERK2 E322K in cancer
- Spred/Sprouty proteins inhibit Ras/ERK pathway
- miR-126 targets Spred-1
- Ubiquitylation
- ERK1/2 and PI3K pathways
- MAPKs are proline-directed kinases
- ERK1/2 scaffolds
- ERK1/2 Bind Microtubules
- ERK1/2 regulate microtubule dynamics
- ERK1/2 and morphology
- Differential localization of ERK1/2
- Function depends on localization
- MAPKs regulate transcription
- Phosphorylation of transcription factors
- ERKs regulate gene transcription
- Output depends on expressed factors
- ChIP-seq analysis of ERK binding
- Acknowledgments
Topics Covered
- MAPK cascade paradigm
- Properties of the MAPK cascade
- ERK1/2 in disease and development
- Activation of the MAPK cascade
- Structure and motifs in the cascade
- Generating specificity in MAPK cascades
- Docking mechanisms
- MAPK scaffolds
- Feedback mechanisms and pathway interactions
- Regulation of the localization of ERK1/2
- MAPKs and transcription
Links
Series:
Categories:
Talk Citation
Cobb, M.H. (2014, December 2). The ERK1/2 MAPK cascade [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 7, 2024, from https://doi.org/10.69645/AQVJ7884.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Melanie H. Cobb has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
A selection of talks on Cell Biology
Transcript
Please wait while the transcript is being prepared...
0:00
This is Melanie Cobb,
and I'll be talking to you about
the ERK1/2 MAP Kinase Pathway.
0:06
The pathway is activated by
many extracellular ligands
and a number of intracellular cues.
0:14
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.
0:32
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.
0:53
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.
1:08
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.