Kinase suppressor of Ras 2

Definition

Location-regulated scaffold connecting MEK to RAF. Has very low protein kinase activity and can phosphorylate MAP2K1 at several Ser and Thr residues with very low efficiency (in vitro). Acts as MAP2K1/MEK1-dependent allosteric activator of BRAF; upon binding to MAP2K1/MEK1, dimerizes with BRAF and promotes BRAF-mediated phosphorylation of MAP2K1/MEK1. Interaction with BRAF enhances KSR2-mediated phosphorylation of MAP2K1 (in vitro). Blocks MAP3K8 kinase activity and MAP3K8-mediated signaling. Acts as a negative regulator of MAP3K3-mediated activation of ERK, JNK and NF-kappa-B pathways, inhibiting MAP3K3-mediated interleukin-8 production.

References:

[1]. Hugo Lavoie, et al. MEK drives BRAF activation through allosteric control of KSR proteins. Nature. 2018 Feb 22;554(7693):549-553. [Content Brief]

[2]. Damian F Brennan, et al. A Raf-induced allosteric transition of KSR stimulates phosphorylation of MEK. Nature. 2011 Apr 21;472(7343):366-9. [Content Brief]

[3]. Padma L Channavajhala, et al. hKSR-2 inhibits MEKK3-activated MAP kinase and NF-kappaB pathways in inflammation. Biochem Biophys Res Commun. 2005 Sep 9;334(4):1214-8. [Content Brief]

[4]. Padma L Channavajhala, et al. Identification of a novel human kinase supporter of Ras (hKSR-2) that functions as a negative regulator of Cot (Tpl2) signaling. J Biol Chem. 2003 Nov 21;278(47):47089-97. [Content Brief]

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