Abstract
The p42 and p44 mitogen-activated protein kinases (MAPKs) (p42/p44 MAPK, Erk2 /Erk1) are activated through the small G protein Ras and sequential activation of the protein kinases Raf and MEK on stimulation of cells with a broad range of extracellular signals (1,2). This signaling pathway, conserved in evolution, controls cell fate, differentiation, proliferation, and cell survival in various invertebrates, mammalian cells, and plants (3–7). To understand the specific role of the commonly expressed and activated p42 and p44 MAPK isoforms in the whole animal, we generated p44 MAPK–deficient mice through homologous recombination in embryonic stem (ES) cells (8). p44 MAPK null mice are viable, fertile, and of normal size. This result indicates that p44 MAPK is dispensable and that the second isoform, p42 MAPK, can compensate for the loss of p44 MAPK. Loss of the p44 MAPK isoform does not affect expression of p42 MAPK in all the tissues tested even in the sciatic nerve, the only tissue in which p44 MAPK is expressed at higher levels than p42 MAPK (1). We previously established that p42/p44 MAPK nuclear translocation (9) and persistent activation during the G1 phase of the cell cycle is a prerequisite for growth control in fibroblasts (10). Thus, it was crucial to analyze the temporal activation of p42/p44 MAPKs and reinitiation of DNA synthesis in wild-type and p44 MAPK–deficient mouse embryo fibroblasts (MEFs). The growth rate as well as reinitiation of DNA synthesis in serum-starved MEFs is not significantly impaired by the ablation of both alleles of p44 MAPK gene (8)
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© 2004 Humana Press Inc., Totowa, NJ
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Pagès, G., Pouysségur, J. (2004). Study of MAPK Signaling Using Knockout Mice. In: Seger, R. (eds) MAP Kinase Signaling Protocols. Methods in Molecular Biology™, vol 250. Humana Press. https://doi.org/10.1385/1-59259-671-1:155
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DOI: https://doi.org/10.1385/1-59259-671-1:155
Publisher Name: Humana Press
Print ISBN: 978-0-89603-998-8
Online ISBN: 978-1-59259-671-3
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