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Mol Cell. 2012 Jul 27;47(2):281-90. doi: 10.1016/j.molcel.2012.05.007. Epub 2012 Jun 7.

Cooperative activation of PI3K by Ras and Rho family small GTPases.

Author information

1
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Republic of Korea.

Abstract

Phosphoinositide 3-kinases (PI3Ks) and Ras and Rho family small GTPases are key regulators of cell polarization, motility, and chemotaxis. They influence each other's activities by direct and indirect feedback processes that are only partially understood. Here, we show that 21 small GTPase homologs activate PI3K. Using a microscopy-based binding assay, we show that K-Ras, H-Ras, and five homologous Ras family small GTPases function upstream of PI3K by directly binding the PI3K catalytic subunit, p110. In contrast, several Rho family small GTPases activated PI3K by an indirect cooperative positive feedback that required a combination of Rac, CDC42, and RhoG small GTPase activities. Thus, a distributed network of Ras and Rho family small GTPases induces and reinforces PI3K activity, explaining past challenges to elucidate the specific relevance of different small GTPases in regulating PI3K and controlling cell polarization and chemotaxis.

PMID:
22683270
PMCID:
PMC3729028
DOI:
10.1016/j.molcel.2012.05.007
[Indexed for MEDLINE]
Free PMC Article

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