Integrin CD11c/CD18 α-Chain Phosphorylation Is Functionally Important

CD11c/CD18 (αXβ2, p150/95, or complement receptor 4, CR4) is a monocyte/macrophage-enriched integrin that has been reported to bind to a variety of ligands. These include cell surface proteins, extracellular matrix proteins, and soluble ligands. The regulation of ligand binding to CD11c/CD18 has remained poorly understood. Previous work has shown that both α-chain and β-chain phosphorylations of CD11a/CD18 and CD11b/CD18 are needed for activity, but no corresponding studies on CD11c/CD18 have been performed. In this study, we have identified the phosphorylation site of CD11c as Ser-1158 and show that it is pivotal for adherence and phagocytosis. Background: Leukocyte integrins are involved in cell adhesion, cell migration, and phagocytosis. Results: CD11c/CD18, a leukocyte integrin expressed on monocytes, macrophages, and dendritic cells, is phosphorylated on Ser-1158 of the α-chain. Abrogation of phosphorylation results in impaired adhesion and phagocytosis. Conclusion: Integrin inside-out activated adhesion is regulated by a single phosphorylation site on CD11c. Significance: Regulation of integrin activity is essential for immune cells.