RalGDS family members couple Ras to Ral signalling and that's not all.

Ras proteins function as molecular switches that are activated in response to signalling pathways initiated by various extracellular stimuli and subsequently bind to numerous effector proteins leading to the activation of several signalling cascades within the cell. Ras and Ras-related proteins belong to a large superfamily of small GTPases characterized by significant sequence and function similarities. Several evidence indicate the existence of complex signalling networks that link Ras with its relatives in the family. A key role in this cross-talk is played by guanine nucleotide exchange factors (GEFs) that serve both as regulators and as effectors of Ras family proteins. The members of the RalGDS family, RalGDS, RGL, RGL2/Rlf and RGL3, can interact with activated Ras through their Ras Binding Domain (RBD), but may function as effectors for other Ras family members. They possess a REM-CDC25 homology region like RasGEFs, but specifically activate only RalA and RalB and not Ras or other Ras-related small GTPases. In this review we provide an update on this recently discovered family of GEFs, highlighting their crucial role in coupling activated Ras to activation of Ral, thus regulating several fundamental cell processes, and also discussing some evidence supporting Ras-independent additional functions of RalGDS proteins.

Ferro E ，Trabalzini L 《-》

Structure determination of the Ras-binding domain of the Ral-specific guanine nucleotide exchange factor Rlf.

Esser D ，Bauer B ，Wolthuis RM ，Wittinghofer A ，Cool RH ，Bayer P ... -  《BIOCHEMISTRY》

A novel potential effector of M-Ras and p21 Ras negatively regulates p21 Ras-mediated gene induction and cell growth.

Ehrhardt GR ，Korherr C ，Wieler JS ，Knaus M ，Schrader JW ... -  《ONCOGENE》

Signaling interplay in Ras superfamily function.

Mitin N ，Rossman KL ，Der CJ 《CURRENT BIOLOGY》

RalGDS-like factor (Rlf) is a novel Ras and Rap 1A-associating protein.

Wolthuis RM ，Bauer B ，van 't Veer LJ ，de Vries-Smits AM ，Cool RH ，Spaargaren M ，Wittinghofer A ，Burgering BM ，Bos JL ... -  《ONCOGENE》