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MAPK signaling:
Preventing tumor cell proliferation

MAPK signaling

The MAPK signaling pathway plays a key role in the regulation of gene expression, cellular growth, and survival. The relationship of MAPK to cancer is an area of intense research at Genentech, a member of the Roche Group.1,2

MAPK Signaling
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MAPK signaling is initiated by receptor tyrosine kinases upon their activation by growth factors in the extracellular space.3 Adaptor molecules that interact directly with the intracellular portion of the receptor mediate the recruitment and activation of signaling molecules of this pathway, which include Ras, Raf, MEK, and ERK, the latter also known as MAPK.1,2

The efficiency and duration of signal transmission is regulated by the protein kinase suppressor of Ras (KSR), which stably associates with MEK and recruits MEK to Raf.4 MEK is a key kinase that forwards upstream signals from Ras and Raf via activation of ERK.1 Once in the nucleus, ERK stimulates multiple transcription factors, resulting in the control of key cellular functions, which can lead to the progression of cancer if abnormally activated.1,5

Through this pathway, abnormal MAPK signaling may lead to1,2

  • Increased/uncontrolled cell proliferation
  • Resistance to apoptosis (programmed cell death)
  • Resistance to chemotherapy, radiotherapy, and targeted therapies
References:
1.
McCubrey JA, Steelman LS, Chappell WH, et al. Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation, and drug resistance. Biochim Biophys Acta. 2007;1773:1263-1284.
2.
Sebolt-Leopold JS, Herrera R. Targeting the mitogen-activated protein kinase cascade to treat cancer. Nat Rev Cancer. 2004;4:937-947.
3.
McCubrey JA, Steelman LS, Abrams SL, et al. Roles of the RAF/MEK/ERK and I3K/PTEN/AKT pathways in malignant transformation and drug resistance. Advan Enzyme Regul. 2006;46:249-279.
4.
Claperón A, Therrien M. KSR and CNK: two scaffolds regulating RAS-mediated RAF activation. Oncogene. 2007;26:3143-3158.
5.
Ussar S, Voss T. MEK1 and MEK2, different regulators of the G1/S transition. J Biol Chem. 2004;279:43861-43869.