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Rac1‐induced cell migration requires membrane recruitment of the nuclear oncogene SET
Author(s) -
ten Klooster Jean Paul,
Leeuwen Ingrid v,
Scheres Nina,
Anthony Eloise C,
Hordijk Peter L
Publication year - 2007
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601518
Subject(s) - biology , microbiology and biotechnology , set (abstract data type) , cell , cell membrane , rac1 , cell nucleus , genetics , signal transduction , nucleus , computer science , programming language
The Rho GTPase Rac1 controls cell adhesion and motility. The effector loop of Rac1 mediates interactions with downstream effectors, whereas its C‐terminus binds the exchange factor β‐Pix, which mediates Rac1 targeting and activation. Here, we report that Rac1, through its C‐terminus, also binds the nuclear oncogene SET/I2PP2A, an inhibitor of the serine/threonine phosphatase PP2A. We found that SET translocates to the plasma membrane in cells that express active Rac1 as well as in migrating cells. Membrane targeting of SET stimulates cell migration in a Rac1‐dependent manner. Conversely, reduction of SET expression inhibits Rac1‐induced migration, indicating that efficient Rac1 signalling requires membrane recruitment of SET. The recruitment of the SET oncogene to the plasma membrane represents a new feature of Rac1 signalling. Our results suggest a model in which Rac1‐stimulated cell motility requires both effector loop‐based downstream signalling and recruitment of a signalling amplifier, that is, SET, through the hypervariable C‐terminus.