Fig. 9

Model for RA-GEF regulation in T cells. In unstimulated cells, RA-GEF is distributed at the cytoplasm, and their phosphorylation/de-phosphorylation at similar residue(s) is co-occurring by WNK1 and other kinases, and PP2A. Gαi protein-coupled receptor (GPCR)-mediated signaling produces PA at the plasma membrane via PLD2, and RA-GEF translocates to the PA-generated region of plasma membrane. GPCR-mediated signaling phosphorylates RA-GEF at different residue(s), which activates RA-GEF. Activated RA-GEF converts Rap1-GDP to Rap1-GTP at PA-concentrated region of the plasma membrane and induces the protrusion, which develops the front membrane