• What is MAP2K1?
  • MAP2K1 in Melanoma
  • Clinical Trials


MEK1 (also known as MAP2K1) is a serine-threonine protein kinase that is a central mediator in the MAP kinase signaling pathway. As part of the MAP kinase pathway, MEK1 is involved in many cellular processes, including cell proliferation, differentiation, and transcriptional regulation.


Figure 1.
Schematic of the MAPK and PI3K pathways. Growth factor binding to receptor tyrosine kinase results in activation of the MAPK signaling pathway (RAS-RAF-MEK-ERK) and the PI3K pathway (PI3K-AKT-mTOR). The letter "K" within the schema denotes the tyrosine kinase domain.

Related Pathways

Contributors: Christine M. Lovly, M.D., Ph.D., Leora Horn, M.D., M.Sc., William Pao, M.D., Ph.D. (through April 2014)

Suggested Citation: Lovly, C., L. Horn, W. Pao. 2015. MEK1 (MAP2K1). My Cancer Genome https://www.padiracinnovation.org/content/disease/melanoma/map2k1/?tab=0 (Updated December 7).

Last Updated: December 7, 2015

MEK1 (MAP2K1) in Melanoma

Somatic mutations in MEK1 have been found in 6–7% of malignant melanomas (COSMIC; Nikolaev et al. 2012). The prevalence of MEK1 mutations in different melanoma subtypes is not yet known. However, most of the reported MEK1 mutations involve C>T and G>A nucleotide changes, which frequently result from exposure to UV radiation (Emery et al. 2009; Nikolaev et al. 2012).

MEK1 mutations often occur together with BRAF or NRAS mutations (Emery et al. 2009; Nikolaev et al. 2012; Shi et al. 2012).

While several MEK inhibitors or multi-kinase inhibitors that target MEK1 are available, little is currently known about the role of MEK1 mutations play in treatment of melanoma (Shi et al. 2012). Some have proposed that MEK1 mutations in BRAF V600E-mutated tumors confer resistance to BRAF inhibition (Emery et al. 2009; Greger et al. 2012; Wagle et al. 2011). However, others have proposed that MEK1 mutations may not play a significant role in sensitivity or resistance to BRAF and MEK1 inhibition (Shi et al. 2012). Clinically, BRAF inhibitors have been investigated in combination with MEK inhibitors in subsets of patients with BRAF V600E mutation-positive melanoma previously resistant to BRAF inhibitors (Johnson et al. 2014; Ribas et al. 2014).

Contributors: Christine M. Lovly, M.D., Ph.D., William Pao, M.D., Ph.D. (through April 2014), Jeff Sosman, M.D.

Suggested Citation: Lovly, C., W. Pao, J. Sosman. 2015. MEK1 (MAP2K1) in Melanoma. My Cancer Genome https://www.padiracinnovation.org/content/disease/melanoma/map2k1/ (Updated June 18).

Last Updated: June 18, 2015

My Cancer Genome has released its new and improved cancer clinical trials search tool on our beta website. Please visit beta.padiracinnovation.org to check it out!

Disclaimer: The information presented at padiracinnovation.org is compiled from sources believed to be reliable. Extensive efforts have been made to make this information as accurate and as up-to-date as possible. However, the accuracy and completeness of this information cannot be guaranteed. Despite our best efforts, this information may contain typographical errors and omissions. The contents are to be used only as a guide, and health care providers should employ sound clinical judgment in interpreting this information for individual patient care.