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Activation of Cdc42 by G proteins

Gα proteins are an important part of the cellular membrane and are actively involved in cell-signaling processes in mammals. They help actin cytoskeleton make cell shape adjustments through activating Rho guanine nucleotide exchange factors, or RhoGEFs. RhoGEFs and the proteins with which they interact could be potential targets for molecules that might prevent the progression of cancer. A study of these cell signaling pathways is essential to develop pharmacological ways that could prevent cancer growth. Alejandro Castillo–Kauil and colleagues at the Vazquez–Prado lab in the Center of Research and Advanced Studies at Mexico's National Polytechnic Institute have tried to understand one such potential cell signaling pathway through investigating the activation of Cdc42 by G proteins.

Gα₁₂ and Gα₁₃ interact with RhoGEFs that drive RhoA activation, but researchers did not know if additional Gα proteins directly regulate these RhoGEFs. Castillo–Kauil and colleagues evaluated the morphological effects of constitutively active constructs from the subfamily of RhoGEFs activated via Gα₁₂ and Gα₁₃. All the constructs promoted cell contraction and activated RhoA, consistent with their known specificity. One of them, PRG, also induced filopodia-like cell protrusions and directly activated Cdc42, an ability that was increased by constitutive active Gαs.

Their results show that Gαs can recognize PRG as a novel effector to gain affinity for Cdc42. Further study of the involvement of this Gs/ PRG/Cdc42 pathway in cell migration could help researchers develop targets that might reduce progression of some cancers.