Inactive RAFs bind YWHAB

Stable Identifier
R-HSA-5672951
Type
Reaction [binding]
Species
Homo sapiens
Compartment
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In quiescent cells, RAF is maintained in a closed state in which the N-terminal regulatory region sterically blocks the catalytic region (Cutler et al, 1998; Tran et al, 2003; Terai et al, 2005; Tran et al, 2005; reviewed in Udell et al, 2011). This closed state is mediated in part by the intramolecular binding of YWHAB/14-3-3 dimers to two phosphorylated serine residues (S259 and S621 in RAF1, S214 and S582 in ARAF and S365 and S729 in BRAF) (Ory et al, 2003; Jaumot et al, 2001; Fischer et al, 2009; reviewed in Udell et al, 2011).

Literature References
PubMed ID Title Journal Year
15711535 Ras binding opens c-Raf to expose the docking site for mitogen-activated protein kinase kinase

Terai, K, Matsuda, M

EMBO Rep. 2005
11494123 Protein phosphatases 1 and 2A promote Raf-1 activation by regulating 14-3-3 interactions

Jaumot, M, Hancock, JF

Oncogene 2001
20820846 Mechanistic principles of RAF kinase signaling

Udell, CM, Rajakulendran, T, Sicheri, F, Therrien, M

Cell. Mol. Life Sci. 2011
15710605 B-Raf and Raf-1 are regulated by distinct autoregulatory mechanisms

Tran, NH, Wu, X, Frost, JA

J. Biol. Chem. 2005
12551923 Phosphorylation of Raf-1 by p21-activated kinase 1 and Src regulates Raf-1 autoinhibition

Tran, NH, Frost, JA

J. Biol. Chem. 2003
12932319 Protein phosphatase 2A positively regulates Ras signaling by dephosphorylating KSR1 and Raf-1 on critical 14-3-3 binding sites

Ory, S, Zhou, M, Conrads, TP, Veenstra, TD, Morrison, DK

Curr Biol 2003
19049963 Regulation of RAF activity by 14-3-3 proteins: RAF kinases associate functionally with both homo- and heterodimeric forms of 14-3-3 proteins

Fischer, A, Baljuls, A, Reinders, J, Nekhoroshkova, E, Sibilski, C, Metz, R, Albert, S, Rajalingam, K, Hekman, M, Rapp, UR

J. Biol. Chem. 2009
9689060 Autoregulation of the Raf-1 serine/threonine kinase

Cutler, RE, Stephens, RM, Saracino, MR, Morrison, DK

Proc. Natl. Acad. Sci. U.S.A. 1998
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