G-protein binding features and regulation of the RalGDS family member, RGL2

Elisa Ferro , David Magrini , Paolo Guazzi , Thomas H Fischer , Sara Pistolesi , Rebecca Pogni , Gilbert C. White Ii , Lorenza Trabalzini (1)

1 Biologia Molecolare

Ral Guanine nucleotide dissociation stimulator-Like 2 (RGL2) is a member of the RalGDS family that we have isolated and characterized as a potential effector for Ras and the Ras analogue Rap1b. The protein shares 89% sequence identity to its mouse orthologue Rlf. In this study we further characterized the G-protein binding features of RGL2 and also demonstrated that RGL2 has guanine nucleotide exchange activity toward the small GTPase RalA. We found that RGL2/Rlf properties are well conserved between human and mouse species. Both RGL2 and Rlf have a putative PKA phosphorylation site at the C-terminal of the domain that regulate the interaction with small GTPases. We demonstrated that RGL2 is phosphorylated by PKA and phosphorylation reduces the ability of RGL2 to bind H-Ras. As RGL2 and Rlf are unique in the RalGDS family in having a PKA site in the Ras Binding Domain, these results indicate that Ras may distinguish between the different RalGDS family members by their phosphorylation by PKA.

Mots clés: Life Sciences

Elisa Ferro, David Magrini, Paolo Guazzi, Thomas H Fischer, Sara Pistolesi, et al.. G-protein binding features and regulation of the RalGDS family member, RGL2. Biochemical Journal, 2008, 415 (1), pp.145-154. ⟨10.1042/BJ20080255⟩. ⟨hal-00478963⟩