2021年9月1日 · Our findings show that as a class, allosteric MEK inhibitors act most potently on BRAF/MEK complexes to block MEK activation, primarily by preventing dual-phosphorylation of MEK S218/S222 by BRAF. Cocrystal structures with the BRAF/MEK complex show that they do so by filling the large preexisting pocket behind the MEK A-loop, where they ...

Because merlin modulates activity of the Ras/Raf/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway, we investigated repurposing drugs targeting MEK1 and/or MEK2 as a treatment for NF2-associated schwannomas.

2018年8月7日 · MAPK/ERK kinase (MEK) 1/2 are central signaling proteins that serve as specificity determinants of the MAPK/ERK cascade. More than twenty activating mutations have been...

2021年7月21日 · mapk通路有三级的信号传递过程：mapk，mapk激酶（mek或mkk）以及mapk激酶的激酶（mekk或mkkk）,这三种激酶能依次激活。 MAPK通路有4种主要的分支路线分别是：

2013年8月11日 · Treatment of KRAS-mutant cells with MEK inhibitors is expected to lead to an increase in phosphorylated MEK (pMEK) through feedback-mediated RAF activation 15,16.

2021年10月7日 · We develop a mechanistic mathematical model that describes how the mutant BRAF inhibitor, dabrafenib, and the MEK inhibitor, trametinib, affect BRAFV600E-MEK-ERK signalling. The model is based...

2021年5月18日 · pMEK and pERK are upregulated in an in vitro BCC model. ERK is the principal target of MEK so why pERK expression is scarce in nBCC is unclear . We examined pMEK and pERK expression in NEB1 keratinocyte cell lines incorporating shRNA targeting PTCH1 (NEB1-shPTCH1) which models nBCC .

2016年10月28日 · The MEK inhibitor trametinib has been shown to increase overall survival in patients with BRAFV600-mutated melanoma and has recently been approved for use in metastatic melanoma. In head and neck cancer, accelerated proliferation in response to ionising radiation through the activation of proliferative signalling pathways might be mitigated ...

Extracellular signal-regulated kinase (ERK), also known as classical mitogen-activated protein kinase, plays critical roles in cell regulation. ERK is activated through phosphorylation by a cascade of protein kinases including MEK. Various ligands activate the MEK/ERK pathway through receptor-dependent cell signaling.

In this study we investigated to what extent the loss of MEK1 and MEK2 contribute to the divergent effects of ERK signaling on either induction or inhibition of cell proliferation in several cell lines. Complete inhibition of MEK1/2 activity with PD184352 resulted in G 1 arrest and induction of apoptosis (8).