Plants integrate external and internal signaling cues to coordinate growth and development. Many of these signaling cues are perceived at the cell surface by plant unique membrane receptor kinases (RKs). Leucine-rich repeat RKs (LRR-RKs) are the most abundant RK family in plants, sensing small molecule, peptide or protein ligands with their extracellular domain. Many LRR-RKs rely on SERK-family co-receptors for receptor activation. How SERKs can contribute to the specific binding of diverse ligands and thus to the activation of different LRR-RKs is poorly understood. The work presented here dissects the contribution of different SERK-interfaces to negative regulation by BIR-proteins as well as to receptor activation. SERKs discriminate ligand-bound and free receptor and thus act as a ‘relay' to transduce a signal across the membrane. These insights into the activation and negative regulation of LRR-RK signaling in mechanistic detail will help to further extend our understanding of RK signaling in plants.