What is PD98059?
PD98059 is a potent and selective cell permeable inhibitor of MAP kinase kinase (MEK). It selectively blocks the activation of MEK, thereby inhibiting the phosphorylation and the activation of MAP kinase.
How does PD98059 work?
PD98059 is a selective, cell permeable inhibitor of the MEK/ERK pathway that acts by preventing the activation of MEK1 (IC₅₀ = 2 – 7 µM) and MEK2 (IC₅₀ = 50 µM) by upstream kinases. It does not inhibit activated MEK, or the p38 MAPK pathway. Blocks the differentiation of mouse ES cells (Burdon et al.).
Why is the MAPK pathway important?
MAPK pathways relay, amplify and integrate signals from a diverse range of stimuli and elicit an appropriate physiological response including cellular proliferation, differentiation, development, inflammatory responses and apoptosis in mammalian cells.
What does RAS do to RAF?
Figure 1. Ras signaling pathways. Ras forms nanoclusters and promotes Raf dimerization in the Raf/MEK/ERK (MAPK) pathway (lower left). Monomeric Raf is autoinhibited in cytosol, and the high-affinity Ras–RBD interaction releases the autoinhibition, activating Raf through side-by-side dimerization.
What is AMPK pathway?
The AMPK signaling pathway AMPK is activated when AMP and ADP levels in the cells rise due to variety of physiological stresses, as well as pharmacological inducers. LKB1 is the upstream kinase activating it in response to AMP increase, whereas CAMKK2 activates AMPK in response to calcium increase.
How does RAS-GTP activate RAF?
In its basal state, RAF is present in a ‘closed’ conformation, wherein the N terminus of the RAF protein interacts with, and inhibits the C terminus. Ligand binding to receptor tyrosine kinase (RTK) results in activation of the RTK, leading to RAS actviation (RAS-GTP).
Does pd98059 (MEK1 inhibitor) act in vivo as a MEK1 inhibitor?
PD98059 (MEK1 Inhibitor) has been shown to act in vivo as a highly selective inhibitor of MEK1 activation and the MAP kinase cascade. In the present study, we have investigated the effects of PD98059, on the development of non-septic shock caused by zymosan in mice.
What does pd98059 do to MEK?
PD98059 is a selective, cell permeable inhibitor of the MEK. PD98059 binds to the inactive form of MEK, thereby preventing the activation of MEK1 ( IC50 =2-7 µM) and MEK2 ( IC50 =50 µM) by upstream kinases. PD98059 causes G1 arrest by blocking p53-dependent p21 induction. For research use only. We do not sell to patients.
Is pd98059 an ERK inhibitor?
PD98059 is a ERK1/2 signaling inhibitor. PD98059 is a ligand for the aryl hydrocarbon receptor (AHR), and suppresses TCDD binding ( IC50 of 4 μM) and AHR transformation ( IC50 of 1 μM). PD98059 also inhibits autophagy [1] [2] [3] .
Does pd98059 inhibit the activity of other protein kinases?
Research studies demonstrate that PD98059 does not inhibit activation of other highly related dual-specificity protein kinases or the activity of more than 18 Ser/Thr protein kinases (3).