Biophysical characterization of MAPK p38 interaction with specific targets

BUCCI, HERNÁN A.; ANGIOLINI, JUAN F.; TURJANSKI, ADRIÁN G.; WETZLER, DIANA E

Congreso; XLV ReuniónAnnual Sociedad Argentina de Biofísica- IX IberoAmerican Congress of Biophysics. III Latin American Federation of Biophysical Societies; 2016

Mitogen activated protein kinases (MAPKs) areserine/threonine kinases that play an important role in regulating variouscellular processes including cell growth, differentiation, inflammation andapoptosis. The development of inhibitors of MAPKs is an important research areafor various diseases such as cancer, diabetes, arthritis and inflammatory diseases.Much effort is being done in searching new compounds or peptides that couldwork as inhibitors.MAPKs utilize a docking strategy to bind its activators,phosphatases, scaffold proteins and its substrates. Linear sequence motifs (thedocking motifs) of the MAPKs interacting partners bind the MAPK at the sameloci outside the active site of their cognate MAPK (the docking groove).Moreover MAPKs usually share upstream kinases or downstream substrates. Thereare still basic questions about the mechanisms that guide the binding ofsubstrates and ATP to MAPKs and the specificity of recognition. In addition, itis not clear whether the dockinginteraction is used only ?to fishing? its substrate andincrease the local concentration of phosphoacceptor site or if it hasadditional allosteric effects on the MAPK enzymatic activity.Focusing on the particular aim of designing specificinhibitors for MAPK p38 we have employed different biophysical techniques tocharacterize in vitro the interaction of this kinase with specific targets. We presenthere some preliminary results that will be useful not only to understand themechanisms of protein-protein recognition in p38 signaling network but also todesign new and specific inhibitors.