title: Role of integrin-linked kinase in leukocyte recruitment.
abstract: Chemokines modulate leukocyte integrin avidity to coordinate adhesion and subsequent transendothelial migration, although the sequential signaling pathways involved remain poorly characterized. Here we show that integrin-linked kinase (ILK), a 59-kDa serine-threonine protein kinase that interacts principally with beta(1) integrins, is highly expressed in human mononuclear cells and is activated by exposure of leukocytes to the chemokine monocyte chemoattractant protein-1. Biochemical inhibitor studies show that chemokine-triggered activation of ILK is downstream of phosphoinositide 3-kinase. In functional assays under physiologically relevant flow conditions, overexpression of wild-type ILK in human monocytic cells diminishes beta(1) integrin/vascular cell adhesion molecule-1-dependent firm adhesion to human endothelial cells. These data implicate ILK in the dynamic signaling events involved in the regulation of leukocyte integrin avidity for endothelial substrates.
authors.affiliation: Center for Immunology and Inflammatory Diseases, Program in Cardiovascular Gene Therapy, Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA.
authors.forename: Erik B
authors.initials: EB
authors.lastname: Friedrich
authors.forename: Sumita
authors.initials: S
authors.lastname: Sinha
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.forename: Shoukat
authors.initials: S
authors.lastname: Dedhar
authors.forename: Thomas
authors.initials: T
authors.lastname: Force
authors.forename: Anthony
authors.initials: A
authors.lastname: Rosenzweig
authors.forename: Robert E
authors.initials: RE
authors.lastname: Gerszten
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002448:Cell Adhesion; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004730:Endothelium, Vascular / Q000166:cytology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D007962:Leukocytes / Q000201:enzymology*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D015398:Signal Transduction; D013997:Time Factors; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D000099200:Scaffold Protein ILK
chemical_list: D018932:Chemokine CCL2; D018076:DNA, Complementary; D004791:Enzyme Inhibitors; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D019010:Vascular Cell Adhesion Molecule-1; D000099200:Scaffold Protein ILK