L-selectin is a type I transmembrane cell adhesion molecule that is expressed on the surface of most circulating leukocytes. Studies in L-selectin knockout mice reveal a prominent role for this glycoprotein in health and disease, regulating leucocyte recruitment to peripheral lymph nodes (e.g. naïve T-cells) and sites of acute and chronic inflammation (e.g. monocytes and neutrophils). Clinical trials have revealed L-selectin as a promising target in some acute and chronic inflammatory diseases. Unearthing the intracellular signals that act directly downstream of L-selectin may also expose novel therapeutic targets in a cell type/disease-specific manner. This review will focus on L-selectin-dependent signalling - exploring the different signals that potentially arise from distinct phases of the multi-step adhesion cascade and the contribution of known binding partners of L-selectin in this response.
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