Reactome | Inactive RAFs bind YWHAB

Inactive RAFs bind YWHAB

Stable Identifier

R-HSA-5672951

Type

Reaction [binding]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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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
11494123	Protein phosphatases 1 and 2A promote Raf-1 activation by regulating 14-3-3 interactions Jaumot, M, Hancock, JF	Oncogene	2001
15711535	Ras binding opens c-Raf to expose the docking site for mitogen-activated protein kinase kinase Terai, K, Matsuda, M	EMBO Rep.	2005
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