Reactome | BRAP binds RAS:GTP

BRAP binds RAS:GTP

Stable Identifier

R-HSA-5674018

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane

ReviewStatus

5/5

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BRAP is a negative regulator of the RAF/MAPK cascade that inhibits the homo- and heterodimerization of KSR1 and RAF and preventing downstream signal propagation (Matheny et al, 2004; Chen et al, 2008; reviewed in Matheny et al, 2009). Upon RAS stimulation, BRAP binds to RAS:GTP. This stimulates BRAP's E3 HECT ubiquitin ligase activity, promoting its autoubiquitination and thereby relieving the inhibition of KSR1 activity (Matheny et al, 2004; reviewed in Matheny et al, 2009). USP15 is a deubiquitinase that stabilizes BRAP protein levels and thus acts to dampen MAPK signaling (Hayes et al, 2013).

Literature References

PubMed ID	Title	Journal	Year
14724641	Ras regulates assembly of mitogenic signalling complexes through the effector protein IMP White, MA, Kortum, RL, Lewis, RE, Razidlo, GL, Matheny, SA, Chen, C	Nature	2004
18332145	IMP modulates KSR1-dependent multivalent complex formation to specify ERK1/2 pathway activation and response thresholds White, MA, Lewis, RE, Chen, C	J. Biol. Chem.	2008
19091743	Signaling threshold regulation by the Ras effector IMP White, MA, Matheny, SA	J. Biol. Chem.	2009
23105109	Direct and indirect control of mitogen-activated protein kinase pathway-associated components, BRAP/IMP E3 ubiquitin ligase and CRAF/RAF1 kinase, by the deubiquitylating enzyme USP15 Clague, MJ, Coulson, JM, MacDonald, E, Sanderson, CM, Urbé, S, Liu, H, Hayes, SD	J. Biol. Chem.	2012