Dbl-related oncoproteins are guanine nucleotide exchange factors (GEFs) specific for Rho-family GTPases and typically possess tandem Dbl (DH) and pleckstrin homology (PH) domains that act in concert to catalyze exchange. The exchange activities of many Dbl-proteins are regulated by phosphorylation or constitutively activated by truncations preceding their DH domains. However, exact mechanisms of regulation remain poorly understood. The current literature regarding the activation and inhibition of the exchange activity of the human Dbl-family proteins is reviewed here, with a focus on general mechanisms of regulation common to many of these proteins.

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