The MEK/ERK cascade: From signaling specificity to diverse functions

Yoav D. Shaul, Rony Seger*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

751 Scopus citations


The ERK signaling cascade is a central MAPK pathway that plays a role in the regulation of various cellular processes such as proliferation, differentiation, development, learning, survival and, under some conditions, also apoptosis. The ability of this cascade to regulate so many distinct, and even opposing, cellular processes, raises the question of signaling specificity determination by this cascade. Here we describe mechanisms that cooperate to direct MEK-ERK signals to their appropriate downstream destinations. These include duration and strength of the signals, interaction with specific scaffolds, changes in subcellular localization, crosstalk with other signaling pathways, and presence of multiple components with distinct functions in each tier of the cascade. Since many of the mechanisms do not function properly in cancer cells, understanding them may shed light not only on the regulation of normal cell proliferation, but also on mechanisms of oncogenic transformation.

Original languageAmerican English
Pages (from-to)1213-1226
Number of pages14
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Issue number8
StatePublished - Aug 2007
Externally publishedYes

Bibliographical note

Funding Information:
We thank Prof. Abraham Amsterdam, Mrs. Tamar Hanoch and Mrs. Marti Spiegel for their help in the preparation of the manuscript. Supported by a grants form La Foundation Raphael et Regina Levi and a grant from the European Community's Sixth Framework Program project IST-2004-027265-SIMAP. Rony Seger is an incumbent of the Yale S. Lewine and Ella Miller Lewine professorial chair for cancer research.


  • ERK
  • MAPK
  • MEK
  • Signaling specificity


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