TY - JOUR
T1 - An MRAS, SHOC2, and SCRIB complex coordinates ERK pathway activation with polarity and tumorigenic growth.
AU - Young, Lucy C
AU - Hartig, Nicole
AU - Muñoz-Alegre, Marta
AU - Oses-Prieto, Juan A
AU - Durdu, Sevi
AU - Bender, Sabine
AU - Vijayakumar, Vineetha
AU - Vietri Rudan, Matteo
AU - Gewinner, Christina
AU - Henderson, Stephen
AU - Jathoul, Amit P
AU - Rodriguez-Viciana, Pablo
PY - 2013/12/12
Y1 - 2013/12/12
N2 - SHOC2 is mutated in Noonan syndrome and plays akey role in the activation of the ERK-MAPK pathway,which is upregulated in the majority of human can-cers. SHOC2 functions as a PP1-regulatory proteinand as an effector of MRAS. Here we show thatSHOC2 and MRAS form a complex with SCRIB, apolarity protein with tumor suppressor properties.SCRIB functions as a PP1-regulatory protein andantagonizes SHOC2-mediated RAF dephosphoryla-tion through a mechanism involving competition forPP1 molecules within the same macromolecularcomplex. SHOC2 function is selectively required forthe malignant properties of tumor cells with mutantRAS, and both MRAS and SHOC2 play a key role inpolarized migration. We propose that MRAS, throughits ability to recruit a complex with paradoxical com-ponents, coordinates ERK pathway spatiotemporaldynamics with polarity and that this complex playsa key role during tumorigenic growth.
AB - SHOC2 is mutated in Noonan syndrome and plays akey role in the activation of the ERK-MAPK pathway,which is upregulated in the majority of human can-cers. SHOC2 functions as a PP1-regulatory proteinand as an effector of MRAS. Here we show thatSHOC2 and MRAS form a complex with SCRIB, apolarity protein with tumor suppressor properties.SCRIB functions as a PP1-regulatory protein andantagonizes SHOC2-mediated RAF dephosphoryla-tion through a mechanism involving competition forPP1 molecules within the same macromolecularcomplex. SHOC2 function is selectively required forthe malignant properties of tumor cells with mutantRAS, and both MRAS and SHOC2 play a key role inpolarized migration. We propose that MRAS, throughits ability to recruit a complex with paradoxical com-ponents, coordinates ERK pathway spatiotemporaldynamics with polarity and that this complex playsa key role during tumorigenic growth.
UR - http://europepmc.org/abstract/med/24211266
U2 - 10.1016/j.molcel.2013.10.004
DO - 10.1016/j.molcel.2013.10.004
M3 - Article
C2 - 24211266
SN - 1097-2765
VL - 52
SP - 679
EP - 692
JO - Molecular Cell
JF - Molecular Cell
ER -
