PI3K is involved in beta 1 integrin clustering by PSGL-1 and promotes beta 1 integrin-mediated Jurkat cell adhesion to fibronectin

P-selectin glycoprotein ligand-1 (PSGL-1) is involved in the initial step of lymphocyte homing by interacting with P- or E-selectins expressed on activated endothelium cells. Besides, it also functions as a receptor to induce signals that increase integrin affinity to ligands and mediate cell adhesion to endothelium. Integrin is required for the second step of lymphocyte homing, whose activation has been reported tightly regulated by inside-out signals triggered by chemokines or the shear-stress generated during lymphocyte rolling on endothelium. However, the relationship between PSGL-1-triggered signals and integrin activation is not clear. In this study, we demonstrated that PSGL-1 ligation induces beta 1 integrin-mediated adhesion to fibronectin via regulation of both beta 1 subunit clustering and conformation changes. Phosphoinositide 3-kinase (PI3K) is required for PSGL-1-induced beta 1 integrin clustering which ultimately regulates beta 1 integrin-mediated Jurkat cell adhesion to fibronectin. However, PI3K is not involved in the conformation changes or increases in the total expression of beta 1 integrin. Taken together, we found a novel signal pathway, PSGL-1-PI3K-beta 1 integrin, demonstrating the cooperation between initial adhesion and subsequent arrest and stable adhesion.