Structural basis for SHOC2 modulation of RAS signalling.

ABSTRACT: The RAS-RAF pathway is one of the most commonly dysregulated in human cancers^1-3. Despite decades of study, understanding of the molecular mechanisms underlying dimerization and activation⁴ of the kinase RAF remains limited. Recent structures of inactive RAF monomer⁵ and active RAF dimer^5-8 bound to 14-3-3^9,10 have revealed the mechanisms by which 14-3-3 stabilizes both RAF conformations via specific phosphoserine residues. Prior to RAF dimerization, the protein phosphatase 1 catalytic subunit (PP1C) must dephosphorylate the N-terminal phosphoserine (NTpS) of RAF¹¹ to relieve inhibition by 14-3-3, although PP1C in isolation lacks intrinsic substrate selectivity. SHOC2 is as an essential scaffolding protein that engages both

SUBMITTER: Liau NPD 

PROVIDER: S-EPMC9452301 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature