Mitogen-activated protein kinases (MAPK) are ancestral kinases that form essential signalling cascades. However, scaffolds that recruit kinases to subcellular locations and promote signal transduction have only been described in few species. Notably, no scaffold was thought necessary for the MAPK c...
CDKs and MAPKs phosphorylate similar sites yet generally have distinct functions/substrates. We report here an unanticipated system of cooperative regulation by CDK and MAPK, involving collaborative multi-site phosphorylation of a single substrate. The budding yeast protein Ste5 is a signaling scaff...
Ste5 and Far1 function as prototypical scaffold proteins activating a MAP-kinase cascade and polarizing yeast cells in response to pheromones. Here we show that Pkc1-dependent phosphorylation of conserved serine residues in their RING-H2 domains down-regulates pheromone induced signaling upon mechan...
MAPK scaffolds, such as IQGAP1, assemble pathway kinases together to effect signal transmission and disrupting scaffold function therefore offers a potentially orthogonal approach to MAPK cascade inhibition. Consistent with this possibility, we observed an IQGAP1 requirement in Ras-driven tumorigene...
MAPK cascade in solution (no scaffold)
Description
This model describes a basic 3-
stage Mitogen Activated Protein Kinase (MAPK)
cascade in solution. This cascade is typ...
MAPK cascade on a scaffold
Citation
Levchenko, A., Bruck, J., Sternberg, P.W. (2000)
.Scaffold proteins may biphasically affect the levels of mitogen-activated protein kinase signaling and reduce its threshold properties. Proc. Natl. Acad. Sci...
Comaprison of the gene expression profiles of the spleen between wild type and Brx haploinsuffieint mice Nuclear factor of activated T-cells 5 (NFAT5) is a transcription factor that regulates hyperosmolarity-responsive genes and helps activated T lymphocytes adapt to and discharge their functions i...
We identified genome-wide binding patterns of CIC in several different cell types and find that CIC target genes are enriched for MAPK effector genes involved in cell cycle regulation and proliferation. CIC binding to its target genes is abolished by high MAPK activity, which leads to hyperacetylati...
