Role of integrin-linked kinase in leukocyte recruitment |
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Authors: | Friedrich Erik B Sinha Sumita Li Ling Dedhar Shoukat Force Thomas Rosenzweig Anthony Gerszten Robert E |
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Institution: | Center for Immunology and Inflammatory Diseases, Program in Cardiovascular Gene Therapy, Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA. |
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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. |
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