Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Sci. Signal., 25 October 2011
Vol. 4, Issue 196, p. re3
[DOI: 10.1126/scisignal.2002324]


Working Without Kinase Activity: Phosphotransfer-Independent Functions of Extracellular Signal–Regulated Kinases

Javier Rodríguez and Piero Crespo*

Instituto de Biomedicina y Biotecnología de Cantabria (IBBTEC), Consejo Superior de Investigaciones Científicas (CSIC)—IDICAN—Universidad de Cantabria. Departamento de Biología Molecular, Facultad de Medicina. Santander, 39011, Cantabria, Spain.

Abstract: The mitogen-activated protein kinases (MAPKs) extracellular signal–regulated kinase 1 (ERK1) and ERK2 play well-characterized roles in the regulation of key cellular processes, such as proliferation, differentiation, and survival, by acting as serine and threonine kinases in the phosphorylation of ~200 substrates that are distributed in different subcellular localizations. However, over the past few years, evidence has mounted that indicates that the mechanism of action of ERK1 and ERK2 may extend beyond their role as canonical kinases. For example, proteins such as poly(ADP-ribose) polymerase 1, topoisomerase II, and MAPK phosphatase 3 (MKP-3) are activated by a direct interaction with ERK2 that does not involve any phosphotransfer activity. In addition, ERK2 binds to DNA and acts as a transcriptional regulator independently of its function as a kinase. Moreover, other studies demonstrate that ERK1 and ERK2 can regulate cell cycle entry by disrupting the interaction between the retinoblastoma pocket protein and lamin A in a kinase-independent fashion. These findings strongly support the notion that ERK1 and ERK2 can play functionally important roles independently of their regular catalytic activities and provide the basis for a new perspective from which to view these hitherto archetypical signaling kinases.

*Corresponding author. E-mail: crespop{at}

Citation: J. Rodríguez, P. Crespo, Working Without Kinase Activity: Phosphotransfer-Independent Functions of Extracellular Signal–Regulated Kinases. Sci. Signal. 4, re3 (2011).

Read the Full Text

Erk1 and Erk2 are required for maintenance of hematopoietic stem cells and adult hematopoiesis.
G. Chan, S. Gu, and B. G. Neel (2013)
Blood 121, 3594-3598
   Abstract »    Full Text »    PDF »
Three-Dimensional Docking in the MAPK p38{alpha}.
E. J. Goldsmith (2011)
Science Signaling 4, pe47
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882