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J Biol Chem. 2004 Oct 15;279(42):43861-9. Epub 2004 Jul 28.

MEK1 and MEK2, different regulators of the G1/S transition.

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  • 1Boehringer Ingelheim Austria GmbH, Dr. Boehringer Gasse 5-11, A-1121 Vienna.

Abstract

The ERK cascade is activated by hormones, cytokines, and growth factors that result in either proliferation or growth arrest depending on the duration and intensity of the ERK activation. Here we provide evidence that the MEK1/ERK module preferentially provides proliferative signals, whereas the MEK2/ERK module induces growth arrest at the G1/S boundary. Depletion of either MEK subtype by RNA interference generated a unique phenotype. The MEK1 knock down led to p21cip1 induction and to the appearance of cells with a senescence-like phenotype. Permanent ablation of MEK1 resulted in reduced colony formation potential, indicating the importance of MEK1 for long term proliferation and survival. MEK2 deficiency, in contrast, was accompanied by a massive induction of cyclin D expression and, thus, CDK4/6 activation followed by nucleophosmin hyperphosphorylation and centrosome over-amplification. Our results suggest that the two MEK subtypes have distinct ways to contribute to a regulated ERK activity and cell cycle progression.

PMID:
15284233
[PubMed - indexed for MEDLINE]
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