Focal Adhesion Kinase–Mediated Activation of Glycogen Synthase Kinase 3β Regulates IL-33 Receptor Internalization and IL-33 Signaling

摘要: IL-33, a relatively new member of the IL-1 cytokine family, plays crucial role in allergic inflammation and acute lung injury. Long form ST2 (ST2L), receptor for is expressed on immune effector cells epithelia critical triggering inflammation. We have previously shown that ST2L stability regulated by ubiquitin-proteasome system; however, its upstream internalization has not been studied. In this study, we demonstrate glycogen synthase kinase 3β (GSK3β) regulates IL-33 signaling. treatment induced internalization, an effect was attenuated inhibition or downregulation GSK3β. GSK3β found to interact with serine residue 446 response treatment. binding site mutant (ST2L S446A ) phosphorylation S442A are resistant IL-33–induced internalization. also activated focal adhesion (FAK). Inhibition FAK impaired activation Furthermore, enhanced release epithelial cells. These results suggest modulation FAK/GSK3β might serve as unique strategy lessen pulmonary