κB‐Ras proteins are fast‐exchanging GTPases and function via nucleotide‐independent binding of Ral GTPase‐activating protein complexes

κB‐Ras (NF‐κB inhibitor‐interacting Ras‐like protein) GTPases are small Ras‐like GTPases but harbor interesting differences in important sequence motifs. They act in a tumor‐suppressive manner as negative regulators of Ral (Ras‐like) GTPase and NF‐κB signaling, but little is known about their mode of function. Here, we demonstrate that, in contrast to predictions based on primary structure, κB‐Ras GTPases possess hydrolytic activity. Combined with low nucleotide affinity, this renders them fast‐cycling GTPases that are predominantly GTP‐bound in cells. We characterize the impact of κB‐Ras mutations occurring in tumors and demonstrate that nucleotide binding affects κB‐Ras stability but is not strictly required for RalGAP (Ral GTPase‐activating protein) binding. This demonstrates that κB‐Ras control of RalGAP/Ral signaling occurs in a nucleotide‐binding‐ and switch‐independent fashion.