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. Author manuscript; available in PMC: 2011 Jul 1.
Published in final edited form as: Clin Cancer Res. 2010 May 14;16(13):3329–3334. doi: 10.1158/1078-0432.CCR-09-3064

Figure 1. The RAS-RAF-MEK-ERK signaling pathway.

Figure 1

The classical MAP kinase pathway is activated in human tumors by several mechanisms including the binding of ligand to receptor tyrosine kinases (RTKs), mutational activation of an RTK, by loss of the tumor suppressor NF1, or by mutations in RAS, BRAF and MEK1. Phosphorylation and thus activation of ERK regulates transcription of target genes which promote cell cycle progression and tumor survival. The ERK pathway contains a classical feedback loop in which the expression of feedback elements such as SPRY and DUSP family proteins are regulated by the level of ERK activity. Loss of expression of SPRY and DUSP family members due to promoter methylation or deletion is thus permissive for persistently elevated pathway output. In the case of tumors with V600EBRAF expression, pathway output is enhanced by impaired upstream feedback regulation.