Single-site or multi-site substitutions test phosphorylation site and coupling site requirements of Opto-mFGFR1. MAPK/ERK pathway activation in HEK293 cells that were transfected with Opto-mFGFR1 harbouring Tyr substitions at positions 81 (463), 201 (583), 203 (585), 348 (730), 384 (766) and 447 (3) or combined substitutions to Ala (‘4A’) at positions K37, P40, L41 and R43 (K419, P422, L423 and R425; numbering is relative to start methionine of Opto-mFGFR1; corresponding positions in mFGFR1 or VfAU1-LOV are given in parentheses). These residues were previously shown to be phosphorylated (Tyr) or required for association of FRS2 (LysProLeuArg).