Étude des kinases RSK : de l’interactome aux fonctions biologiques
The Ras/MAPK signaling pathway regulates many biological functions and plays a key role in transducing extracellular signals to intracellular target proteins. Inappropriate regulation of this pathway leads to a variety of diseases and genetic syndromes, including cancer or diabetes. This signaling pathway regulates the activity of ERK1/2 protein kinases, which have many cellular substrates, and therefore regulates significant biological processes. Among these substrates, there is the RSK (p90 ribosomal S6 kinase) family of protein kinases, which is composed of four isoforms (RSK1-4). Although several cellular substrates have been identified for the RSK1 and RSK2 isoforms, the biological functions of RSK kinases and the molecular mechanisms regulating them are still poorly understood. Thus, to improve our knowledge of the RSK family, we used several approaches. First, we determined the cellular partners of the RSK kinases using a proximity-based labeling technique. This first step allowed us to identify the p120ctn protein as a new substrate of RSK kinases, but also to demonstrate the role of these proteins in the regulation of intercellular junction’s integrity. Additionally, by focusing on a particular domain of RSK kinases still unstudied, our second study also provided new insights into the different interactions of RSK proteins. Finally, we demonstrated that the binding of the RSK2 isoform with the Scribble protein inhibits its activation by the Ras/MAPK signaling pathway. Consequently, by establishing large-scale studies to determine the specific interactions of each RSK isoform, we have identified several new cellular partners of these proteins and their associated functions. This step is crucial to understand and characterize the role of the RSK proteins, particularly with respect to their described functions in cancer.
phosphorylation cancer RSK MAPK p120ctn Scribble cell signaling intercellular junctions