Summary 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 …

Class I Phosphoinositide 3-kinases (PI3Ks) and Ras and Rho family small GTPases are key
regu-lators of processes such as cell polarization, motility and chemotaxis. Class I PI3Ks are
comprised of four p110 catalytic subunits (p110α, p110β, p110γ, and p110δ). These
signaling components influence each other's activities by direct and indirect feedback
processes that are only partially understood. A number of studies have shown that PI3Ks are
activated by Ras and Rho family small GTPases, but little is known about isoform-specific …