Reactome | RAF phosphorylates MAP2K dimer

RAF phosphorylates MAP2K dimer

Stable Identifier

R-HSA-5672978

Type

Reaction [transition]

Species

Homo sapiens

Compartment

plasma membrane

ReviewStatus

5/5

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Activated RAF phosphorylates the MEK kinases MAP2K1 and MAP2K2 on 2 serine residues in the MAP2K activation loop (S218 and S222 in MAP2K1 and S222 and S226 in MAP2K2 (Zheng and Guan, 1994; Alessi et al, 1994; Catling et al, 1995; Papin et al, 1995; Seger et al, 1994; reviewed in Roskoski, 2012a). Although all three RAF kinases can phosphorylate MAP2K1 and MAP2K2, BRAF appears to be the primary activator in vivo (Marais et al, 1997; Jaiswal et al, 1994; Pritchard et al, 1995; reviewed in Welbrock et al, 2004)

Literature References

PubMed ID	Title	Journal	Year
22177953	MEK1/2 dual-specificity protein kinases: structure and regulation Roskoski, R Jr	Biochem. Biophys. Res. Commun.	2012
7565795	Conditionally oncogenic forms of the A-Raf and B-Raf protein kinases display different biological and biochemical properties in NIH 3T3 cells Pritchard, CA, Samuels, ML, Bosch, E, McMahon, M	Mol. Cell. Biol.	1995
7929275	Overexpression of mitogen-activated protein kinase kinase (MAPKK) and its mutants in NIH 3T3 cells. Evidence that MAPKK involvement in cellular proliferation is regulated by phosphorylation of serine residues in its kinase subdomains VII and VIII. Seger, R, Seger, D, Reszka, AA, Munar, ES, Eldar-Finkelman, H, Dobrowolska, G, Jensen, AM, Campbell, JS, Fischer, EH, Krebs, EG	J Biol Chem	1994
7565670	A proline-rich sequence unique to MEK1 and MEK2 is required for raf binding and regulates MEK function. Catling, AD, Schaeffer, HJ, Reuter, CW, Reddy, GR, Weber, MJ	Mol Cell Biol	1995
7731720	B-Raf protein isoforms interact with and phosphorylate Mek-1 on serine residues 218 and 222. Papin, C, Eychène, A, Brunet, A, Pagès, G, Pouysségur, J, Calothy, G, Barnier, JV	Oncogene	1995
9020159	Differential regulation of Raf-1, A-Raf, and B-Raf by oncogenic ras and tyrosine kinases Marais, R, Light, Y, Paterson, HF, Mason, CS, Marshall, CJ	J. Biol. Chem.	1997
7935411	The mitogen-activated protein kinase cascade is activated by B-Raf in response to nerve growth factor through interaction with p21ras Jaiswal, RK, Moodie, SA, Wolfman, A, Landreth, GE	Mol. Cell. Biol.	1994
8051079	Cytoplasmic localization of the mitogen-activated protein kinase activator MEK Zheng, CF, Guan, KL	J. Biol. Chem.	1994
8157000	Identification of the sites in MAP kinase kinase-1 phosphorylated by p74raf-1 Alessi, DR, Saito, Y, Campbell, DG, Cohen, P, Sithanandam, G, Rapp, U, Ashworth, A, Marshall, CJ, Cowley, S	EMBO J.	1994