Leucine-rich repeat scaffold protein SHOC2 (SHOC2)

Leucine-rich repeat scaffold protein SHOC2 is a highly conserved scaffold protein that integrates signals between RAS GTPases and RAF kinases in the ERK1/2 (MAPK) signaling cascade[1][2][3]. SHOC2 forms a ternary holophosphatase complex with the catalytic subunit of protein phosphatase 1 (PP1C) and GTP-bound MRAS (and to a lesser extent canonical RAS isoforms), facilitating the dephosphorylation of an inhibitory serine (S259) on RAF kinases[2][6][7]. This process is essential for proper MAPK signal propagation, cellular differentiation, and proliferation. Pathogenic variants in SHOC2 cause developmental syndromes (notably, RASopathies including Noonan-like syndrome with loose anagen hair), and its upregulation or mutation can contribute to cancer progression by enhancing ERK pathway activation[3][5]. The SHOC2 complex thus represents a critical node in MAPK pathway regulation and a potential, though challenging, therapeutic target[5][7].

Other names

Leucine-rich repeat protein SHOC-2KIAA0862SOC2SUR-8SUR8Protein soc-2 homologProtein sur-8 homologNSLH1SIAA0862soc-2 suppressor of clear homolog

Facilitates dephosphorylation of RAF at S259 by bringing together RAS (GTP-bound) and PP1C, enabling MAPK pathway activation[7][3][2]. Drugs or modulators would theoretically act by disrupting SHOC2-RAS-PP1C complex assembly, scaffolding function, or its recruitment to the membrane.