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From RAS to MAPK: Cell-Free Assay System for RAS- and Rap1–Dependent B-Raf Activation

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Regulation of the RAS Signaling Network

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Abstract

It is well established that RAS activates the MAP kinase cascade, consisting of the mitogen-activated protein (MAP) kinase/extracellular signal-regulated kinase (ERK), ERK kinase (MEK) and MEK kinase in mammals (for reviews, see refs. 1–4). MAP kinase is phosphorylated at both serine/threonine and tyrosine residues by MEK, and this phosphorylation causes MAP kinase activation.1–3 MEK is also phosphorylated at serine/threonine residues by MEK kinase and this phosphorylation causes MEK activation.5–7 Many MEK kinases have been identified: these include c-Raf-1,8–10 B-Raf,11–15 Mos16,17 and mStell.11,18 There are several lines of evidence that RAS is an upstream regulator of c-Raf-1: (i) anti-sense c-Raf-1 RNA and dominant negative c-Raf-1 inhibit the RAS-induced DNA synthesis and growth;19 (ii) RAS genetically positions upstream of c-Raf-1 in Drosophila 20 and Caenorhabditis elegans;21 (iii) dominant negative c-Raf-1 inhibits the RAS-induced MAP kinase activation in intact cells;22 and (iv) GTP-RAS directly interacts with c-Raf-1.23–28

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  1. Kazuya Shimizu
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  2. Toshihisa Ohtsuka
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  3. Yoshimi Takai
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Shimizu, K., Ohtsuka, T., Takai, Y. (1996). From RAS to MAPK: Cell-Free Assay System for RAS- and Rap1–Dependent B-Raf Activation. In: Regulation of the RAS Signaling Network. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-1183-6_6

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  • DOI: https://doi.org/10.1007/978-1-4613-1183-6_6

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