In plants, receptor-like kinases (RLKs) form the largest family of membrane receptors (>400) and they are involved in virtually all aspects of the plant life cycle, including development, immunity and reproduction. Although a few model RLKs, such as the steroid receptor BRI1, have been studied extensively, there are still many with unknown function. Besides, we still know very little on how those receptors are activated. Notably, the functions and mechanisms of RLK negative regulation have virtually not been addressed, while it is established that receptor inhibition play a critical role in signaling and diseases in metazoan. During my postdoctoral work, I characterized a negative regulator of BRI1 called BKI1 (for BRI1 KINASE INHIBITOR) and identified a small family of related proteins of unknown function, called MAKRs for MEMBRANE ASSOCIATED KINASE REGULATORs. Preliminary results suggest that some MAKR proteins regulate BRI1, while others control different developmental pathways, possibly regulated by unknown RLKs. Here we propose to combine biochemistry, genetic and cell biology to address the mechanisms by which BKI1/MAKRs regulate RLK activity and to identify the developmental pathways and receptors targeted by the MAKR proteins. This work should unravel the functions of RLK negative regulation as well as identify new receptor kinase involved in plant development. Altogether, our studies will provide mechanistic insight into receptor kinase signaling pathways in plant and their evolutionary relationship to well-studied mammalian systems.