Chiara Vantaggiato, Ivan Formentini and colleagues in Riccardo Brambilla's group, from the San Raffaele Scientific Institute in Milan, Italy, used gene targeting and RNA interference (RNAi) techniques to inhibit the MAP kinases ERK1 and ERK2 in mouse cells. Their results show that inhibiting ERK1 enhances ERK2 activity and promotes cell proliferation. In contrast, the knockdown of ERK2 almost completely abolishes cell proliferation. Mouse tumour cells expressing ERK1, but not ERK2, to higher levels than normally seen in tumour cells, grow into very small tumours when transplanted into live mice. Cells expressing only the protein Ras grow into much larger tumours and overexpressing ERK2 doesn't affect the size of the tumours.
The authors propose that ERK1 and ERK2 are in competition to bind to other regulatory molecules in the signalling pathway. Their activities and expression levels must be finely tuned to ensure normal cell proliferation.
Article:
ERK1 and ERK2 mitogen-activated protein kinases affect Ras-dependent cell signaling differentially
Chiara Vantaggiato, Ivan Formentini, Attilio Bondanza, Chiara Bonini, Luigi Naldini and Riccardo Brambilla
Journal of Biology 2006, 5:14 (to be published 28 June 2006)
Journal of Biology