Reactome | PEBP1 binds activated RAF1

PEBP1 binds activated RAF1

Stable Identifier

R-HSA-5675417

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane

ReviewStatus

5/5

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PEBP1, also known as RKIP (Raf kinase inhibitor protein), is a negative regulator of RAF1 that binds to the phosphorylated NtA region and prevents activation of MAP2K substrates (Yeung et al, 1999; Yeung et al, 2000; Rath et al, 2008; Park et al, 2006; reviewed in Lorenz et al, 2014). Relief of this PEBP1 repression of RAF1 activity is stimulated by phosphorylation of PEBP1, which promotes it dissociation from RAF1. Candidate kinases for phosphorylation of PEBP1 include PKC and the MAPKs themselves, which would establish a positive feedback loop stimulating MAPK pathway activity (Corbit et al, 2003; Cho et al, 2003; Shin et al, 2009).

Literature References

PubMed ID	Title	Journal	Year
17097642	Regulation of RKIP binding to the N-region of the Raf-1 kinase Park, S, Rath, O, Beach, S, Xiang, X, Kelly, SM, Luo, Z, Kolch, W, Yeung, KC	FEBS Lett.	2006
25597358	RKIP: a governor of intracellular signaling Lorenz, K, Schmid, E, Deiss, K	Crit Rev Oncog	2014
10757792	Mechanism of suppression of the Raf/MEK/extracellular signal-regulated kinase pathway by the raf kinase inhibitor protein Yeung, K, Janosch, P, McFerran, B, Rose, DW, Mischak, H, Sedivy, JM, Kolch, W	Mol. Cell. Biol.	2000
18294816	The RKIP (Raf-1 Kinase Inhibitor Protein) conserved pocket binds to the phosphorylated N-region of Raf-1 and inhibits the Raf-1-mediated activated phosphorylation of MEK Rath, O, Park, S, Tang, HH, Banfield, MJ, Brady, RL, Lee, YC, Dignam, JD, Sedivy, JM, Kolch, W, Yeung, KC	Cell. Signal.	2008
19158341	Positive- and negative-feedback regulations coordinate the dynamic behavior of the Ras-Raf-MEK-ERK signal transduction pathway Shin, SY, Rath, O, Choo, SM, Fee, F, McFerran, B, Kolch, W, Cho, KH	J. Cell. Sci.	2009
10490027	Suppression of Raf-1 kinase activity and MAP kinase signalling by RKIP Yeung, K, Seitz, T, Li, S, Janosch, P, McFerran, B, Kaiser, C, Fee, F, Katsanakis, KD, Rose, DW, Mischak, H, Sedivy, JM, Kolch, W	Nature	1999