The coordinated biology and signaling partners of Ral G-proteins

The Ras-like (Ral) guanyl nucleotide-binding proteins, RALA and RALB, are highly similar proteins, which occupy sometimes overlapping, convergent, or divergent roles in regulating distinct biological processes. As downstream signaling partners of oncogenic Ras, these two proteins have been described to be hyper-activated in tumors to support aberrant biology during oncogenic transformation. To regulate a varied collection of normal and oncogenic biological processes, Ral G-proteins engage with six upstream RalGEF proteins, two upstream RalGAP complexes, and at least five distinct downstream effector pathways. Further specification of Ral signaling activity is ascribed to distinct posttranslational modifications of RALA, RALB, their upstream regulators, and their effectors. Emerging signaling paradigms within Ral signaling networks provide important insight into the signaling architectures exhibited by not only Ral G-proteins but also the wider range of Ras superfamily small G-proteins as well.