14-3-3zeta Regulates Transmembrane Receptor Signaling by Binding TRAF Proteins

Abstract Adaptor proteins are critical for signal transduction events involving cytokine signaling, host-response, and autoimmune diseases. Our laboratory is interested in understanding the immune regulatory role of 14-3-3zeta (z), an adaptor protein, transductions We examined 14-3-3z interleukin-17 (IL-17A) signaling inflammatory arthritis using genetically modified cells rats. The IL-17A requires IL-17 receptor cytoplasmic domain interactions with Act1 several TRAF proteins. results show that interacts TRAF6, TRAF2, TRAF5 upon stimulation which has functional consequences. interaction protein was found to be specific, as mutation interacting residues resulted loss binding impacts. Further studies a higher affinity two putative 14-3-3 sites. To examine generality 14-3-3z-TRAF their another transmembrane we RANKL transduction. Similar IL-17A, increased treatment had While there common domains significant sequence conservation between proteins, specificity exists 14-3-3z. axis novel mechanism underneath receptor-mediated signaling. Current target molecular basis specific