PEBP1 binds activated RAF1

Stable Identifier
R-HSA-5675417
Type
Reaction [binding]
Species
Homo sapiens
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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
25597358 RKIP: a governor of intracellular signaling

Lorenz, K, Schmid, E, Deiss, K

Crit Rev Oncog 2014
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
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
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