A mechanistic view of flg22 sensing by FLS2. flg22 (light green) stabilizes the heterodimerization of FLS2 (dark green, PDB entries 4NMA and 4NM8) with BAK1 (purple, PDB entries 3ULZ and 4NM8) (82, 85, 86). Ligand perception leads to activation and phosphorylation of BIK1 (orange, PDB entry 5TOS) by BAK1 (87, 88). Following phosphorylation, BIK1 is monoubiquitinated (Ub) by the E3 ligases RHA3A/B. Monoubiquitinated BIK1 is then released from the FLS2–BAK1 complex and initiates ROS production and Ca2+ signaling through phosphorylation of plasma membrane–localized NADPH oxidases and cyclic nucleotide–gated channels (89). The bidirectional arrow indicates that both BIK1 and BAK1 can trans-phosphorylate each other.