title: PI3K is involved in β1 integrin clustering by PSGL-1 and promotes β1 integrin-mediated Jurkat cell adhesion to fibronectin.
abstract: 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 β1 integrin-mediated adhesion to fibronectin via regulation of both β1 subunit clustering and conformation changes. Phosphoinositide 3-kinase (PI3K) is required for PSGL-1-induced β1 integrin clustering which ultimately regulates β1 integrin-mediated Jurkat cell adhesion to fibronectin. However, PI3K is not involved in the conformation changes or increases in the total expression of β1 integrin. Taken together, we found a novel signal pathway, PSGL-1-PI3K-β1 integrin, demonstrating the cooperation between initial adhesion and subsequent arrest and stable adhesion.
authors.forename: Jixian
authors.initials: J
authors.lastname: Luo
authors.forename: Chunfeng
authors.initials: C
authors.lastname: Li
authors.forename: Tingshuang
authors.initials: T
authors.lastname: Xu
authors.forename: Wenai
authors.initials: W
authors.lastname: Liu
authors.forename: Xueqing
authors.initials: X
authors.lastname: Ba
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Wang
authors.forename: Xianlu
authors.initials: X
authors.lastname: Zeng
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D016000:Cluster Analysis; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D055767:Immobilized Proteins / Q000494:pharmacology; D019012:Integrin beta1 / Q000378:metabolism*; D019169:Jurkat Cells; D008562:Membrane Glycoproteins / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*
chemical_list: D005353:Fibronectins; D055767:Immobilized Proteins; D019012:Integrin beta1; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D019869:Phosphatidylinositol 3-Kinases