Abstract 4045: MRAS and SHOC2 interact with SCRIB and coordinate ERK pathway activation with polarity and tumorigenic growth

SHOC2 is mutated in Noonan syndrome and plays a key role in the activation of the ERK-MAPK pathway, which is upregulated in the majority of human cancers. SHOC2 functions as a PP1-regulatory protein and as an effector of MRAS. Here we show that SHOC2 and MRAS form a complex with SCRIB, a polarity protein with tumor suppressor properties. SCRIB functions as a PP1-regulatory protein and antagonizes SHOC2-mediated RAF dephosphorylation through a mechanism involving competition for PP1 molecules within the same macromolecular complex. SHOC2 function is selectively required for the malignant properties of tumor cells with mutant RAS, and both MRAS and SHOC2 play a key role in polarized migration. We propose that MRAS, through its ability to recruit a complex with paradoxical components, coordinates ERK pathway spatiotemporal dynamics with polarity and that this complex plays a key role during tumorigenic growth. Citation Format: Lucy C. Young, Nicole Hartig, Marta Munoz-Alegre, Juan A. Oses-Prieto, Sevi Durdu, Sabine Bender, Vineetha Vijakumar, Matteo Vietri Rudan, Christina Gewinner, Amit P. Jathoul, Rupinder Ghatrora, Mark L. Lythgoe, Alma L. Burlingame, Pablo Rodriguez-Viciana. MRAS and SHOC2 interact with SCRIB and coordinate ERK pathway activation with polarity and tumorigenic growth. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4045. doi:10.1158/1538-7445.AM2015-4045