2015年9月24日 · New drugs that inhibit RAF or MEK1 and MEK2 have recently been approved or are currently undergoing late-stage clinical evaluation. In this Review, we consider the ERK pathway, focusing...

2004年11月14日 · Here we present the X-ray structures of human MEK1 and MEK2, each determined as a ternary complex with MgATP and an inhibitor to a resolution of 2.4 Å and 3.2 Å, respectively. The structures...

2012年1月6日 · MEK1 and MEK2 are related protein kinases that participate in the RAS-RAF-MEK-ERK signal transduction cascade. This cascade participates in the regulation of a large variety of processes including apoptosis, cell cycle progression, cell migration, differentiation, metabolism, and proliferation.

This demonstrates the pivotal roles of MEK1/2 in malignant transformation, rationalizing therapeutic targeting of upregulated MEK1/2 activity in cancer. In addition, there are unique characteristics of MEK1 and MEK2 that might support the advantage of therapeutic development of MEK1/2 inhibition.

New drugs that inhibit RAF or MEK1 and MEK2 have recently been approved or are currently undergoing late-stage clinical evaluation. In this Review, we consider the ERK pathway, focusing particularly on the role of MEK1 and MEK2, the 'gatekeepers' of ERK1/2 activity.

Four distinct MAP kinase signaling pathways involving 7 MEK enzymes have been identified. MEK1 and MEK2 are the prototype members of MEK family proteins. Several MEK inhibitors are in clinical trials. Trametinib is being evaluated by FDA for the treatment of metastatic melanoma.

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 reported for MEK1/2,...

MEK2 is a critical modulating mechanism to down-regulate GCIP stability and function in cancer cells. USP21-mediated deubiquitination and stabilization of MEK2 plays a critical role in hepatocellular carcinoma development.

2012年1月6日 · MEK1/2 are dual-specificity protein kinases that mediate the phosphorylation of tyrosine and then threonine in ERK1 or ERK2, their only known physiological substrates. This phosphorylation activates ERK1/2, which are protein-serine/threonine kinases.

2015年7月20日 · In this paper, we found that the expression of MEK2 in primary glioma was upregulated and was correlated with glioma grades and the outcome of TMZ treatment. We further revealed that downregulation of MEK2 inhibited the ERK1/2 pathway and sensitized glioma cells to TMZ treatment.

Here we present the X-ray structures of human MEK1 and MEK2, each determined as a ternary complex with MgATP and an inhibitor to a resolution of 2.4 A and 3.2 A, respectively. The structures reveal that MEK1 and MEK2 each have a unique inhibitor-binding pocket adjacent to the MgATP-binding site.

2021年1月5日 · MEK proteins are coded by 7 different genes, among which MEK1 and MEK2 are of significance. MEK1 gene exists in human chromosome 15q22.31, and MEK2 gene exists in chromosome 9q13.3 [11].

2024年12月25日 · MAP2K2 (Mitogen-Activated Protein Kinase Kinase 2) is a Protein Coding gene. Diseases associated with MAP2K2 include Cardiofaciocutaneous Syndrome 4 and Cardiofaciocutaneous Syndrome. Among its related pathways are Prolactin Signaling and IL-9 Signaling Pathways.

2014年5月20日 · Highly selective and potent non-ATP-competitive allosteric MEK1/2 inhibitors have been developed and assessed in numerous clinical studies over the past decade.

2010年2月11日 · In this article, we briefly review the basic research that has laid the groundwork for the clinical development of small molecules inhibitors of the ERK1/2 pathway. We then present the current state of clinical evaluation of MEK1/2 inhibitors in …

2022年1月11日 · MEK1 and MEK2, the only known activators of ERK, are attractive therapeutic candidates for both cancer and autoimmune diseases. However, how MEK signaling finely regulates immune cell activation is only partially understood. To address this question, we specifically delete Mek1 in hematopoietic cells in the Mek2 null background.

2013年4月12日 · Four distinct MAP kinase signaling pathways involving 7 MEK enzymes have been identified. MEK1 and MEK2 are the prototype members of MEK family proteins. Several MEK inhibitors are in clinical trials. Trametinib is being evaluated by FDA for the treatment of metastatic melanoma.

The MAP2K2 gene provides instructions for making a protein known as MEK2 protein kinase. This protein is part of a signaling pathway called the RAS/MAPK pathway, which transmits chemical signals from outside the cell to the cell's nucleus.

MEK1 is a dual specificity kinase that phosphorylates and activates the Erk/MAP kinases Erk-1 and Erk-2 by phosphorylating them on threonine and tyrosine. We report the cloning of a second MEK-like complementary DNA, Mek2, which predicts a protein of a molecular weight of 44,500.

Our results suggest that the two MEK subtypes have distinct ways to contribute to a regulated ERK activity and cell cycle progression. The extracellular-regulated kinase (ERK) 1 cascade is one of three major mitogen-activated protein kinase cascades.