An MRAS, SHOC2, and SCRIB Complex Coordinates ERK Pathway Activation with Polarity and Tumorigenic Growth

被引：94

作者：

Young, Lucy C. ^{[1
]}

Hartig, Nicole ^{[1
]}

Munoz-Alegre, Marta ^{[1
]}

Oses-Prieto, Juan A. ^{[2
]}

Durdu, Sevi ^{[3
]}

Bender, Sabine ^{[1
]}

Vijayakumar, Vineetha ^{[4
]}

Rudan, Matteo Vietri ^{[1
]}

Gewinner, Christina ^{[1
]}

Henderson, Stephen ^{[1
]}

Jathoul, Amit P. ^{[1
]}

Ghatrora, Rupinder ^{[5
,6
]}

Lythgoe, Mark F. ^{[5
,6
]}

Burlingame, Alma L. ^{[2
]}

Rodriguez-Viciana, Pablo ^{[1
]}

机构：

[1] UCL, UCL Canc Inst, London WC1E 6BT, England

[2] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 USA

[3] European Mol Biol Lab, D-69117 Heidelberg, Germany

[4] Kings Coll London, Randall Div Cell & Mol Biophys, London SE1 1UL, England

[5] UCL, UCL Ctr Adv Biomed Imaging, Div Med, London WC1E 6BT, England

[6] UCL, Inst Child Hlth, London WC1E 6BT, England

来源：

MOLECULAR CELL | 2013年 / 52卷 / 05期

关键词：

RICH REPEAT PROTEIN; CELL POLARITY; MESENCHYMAL TRANSITION; M-RAS; CANCER; PHOSPHATASE-1; FAMILY; EXPRESSION; MIGRATION; EFFECTOR;

D O I：

10.1016/j.molcel.2013.10.004

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：679 / 692

页数：14

共 43 条

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