The ins and outs of leukocyte integrin signaling.
Integrins are the principal cell adhesion receptors that mediate leukocyte migration and activation in the immune system. These receptors signal bidirectionally through the plasma membrane in pathways referred to as inside-out and outside-in signaling. Each of these pathways is mediated by conformational changes in the integrin structure. Such changes allow high-affinity binding of the receptor with counter-adhesion molecules on the vascular endothelium or extracellular matrix and lead to association of the cytoplasmic tails of the integrins with intracellular signaling molecules. Leukocyte functional responses resulting from outside-in signaling include migration, proliferation, cytokine secretion, and degranulation. Here, we review the key signaling events that occur in the inside-out versus outside-in pathways, highlighting recent advances in our understanding of how integrins are activated by a variety of stimuli and how they mediate a diverse array of cellular responses.
Abram
Clare L
CL
Program in Immunology, Department of Laboratory Medicine, University of California, San Francisco, California 94143-0451, USA.
Lowell
Clifford A
CA
D000595:Amino Acid Sequence; D000818:Animals; D002465:Cell Movement; D003599:Cytoskeleton / Q000276:immunology / Q000378:metabolism; D042783:Endothelial Cells / Q000276:immunology* / Q000378:metabolism; D005109:Extracellular Matrix / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D011494:Protein Kinases / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D020668:rap GTP-Binding Proteins / Q000276:immunology / Q000378:metabolism
D016023:Integrins; D011494:Protein Kinases; D020668:rap GTP-Binding Proteins