TY  - JOUR
AU  - Rasche, René
AU  - Apken, Lisa Helene
AU  - Titze, Sonja
AU  - Michalke, Esther
AU  - Singh, Rohit Kumar
AU  - Oeckinghaus, Andrea
AU  - Kuemmel, Daniel
TI  - The GTPase κB-Ras is an essential subunit of the RalGAP tumor suppressor complex
JO  - JBC papers in press
VL  - 301
IS  - 8
SN  - 0021-9258
CY  - Bethesda, MD
PB  - American Soc. for Biochemistry and Molecular Biology
M1  - PUBDB-2025-04141
SP  - 110460 
PY  - 2025
N1  - ISSN 0021-9258 not unique: **2 hits**.   This work was supported bygrants from Deutsche Forschungsgemeinschaft (DFG, GermanResearch Foundation; grant no.: KU2531/6-1; to D. K. and grantno.: OE531/4-1; to A. O.).
AB  - κB-Ras1 and κB-Ras2 are small GTPases with noncanonical features that act as tumor suppressors downstream of Ras. Via interaction with the RalGAP (GTPase-activating protein) complex, they limit activity of Ral GTPases and restrict anchorage-independent proliferation. We here present the crystal structure of κB-Ras1 in complex with the N-terminal domain of RGα2. The structure suggests a mechanism of intrinsic GTP hydrolysis of κB-Ras1 that relies on a scaffolding function of the GTPase rather than on catalytic residues, which we confirm by mutational analysis. The interaction with RGα2 is nucleotide independent and does not involve κB-Ras1 switch regions, which establishes κB-Ras proteins as a constitutive third subunit of RalGAP complexes. Functional studies demonstrate that κB-Ras proteins are not required for RalGAP catalytic activity in vitro but for functionality in vivo. We propose that κB-Ras may thus act as a regulator of RalGAP localization and thereby control the Ras–Ral signaling pathway.
LB  - PUB:(DE-HGF)16
DO  - DOI:10.1016/j.jbc.2025.110460
UR  - https://bib-pubdb1.desy.de/record/638674
ER  -