RGL2 (RalGDS-like 2) belongs to the Ral GDP dissociation stimulator (RalGDS) family []. The C-terminal fragment (Ras/Rap-binding domain) of RGL2 interacts specifically with Ras family proteins that share identical effector domain sequences with Rap1 (H-Ras, R-Ras, Tc21). The binding ability of RGL2 to H-Ras can be regulated through a PKA phosphorylation site identified in this C-terminal domain []. This phoshorylation site is only conserved in the RGL2 murine orthologue, Rlf, but not in RalGDS, RGL and RGL3 []. RGL2 is a guanine nucleotide exchange factor (GEF) for RalA, which plays an important role in the assembly of the exocyst complex. R-Ras regulates exocytosis by RGL2/Rlf-mediated activation of RalA on endosomes [].RalGDS family members can act both as Ras effectors and as guanine nucleotide exchange factors (GEFs) for Ral. They act downstream of Ras and bind to the GTP-bound active form of Ras or Ras family members. They also promote the GDP to GTP exchange for Ral small GTPase, member of the Ras family []. Due to their double action, the RalGDS proteins bridge Ras and Ral [].
