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  • A guide to chemokines and t...
    Hughes, Catherine E.; Nibbs, Robert J. B.

    The FEBS journal, August 2018, Letnik: 285, Številka: 16
    Journal Article

    The chemokines (or chemotactic cytokines) are a large family of small, secreted proteins that signal through cell surface G protein‐coupled heptahelical chemokine receptors. They are best known for their ability to stimulate the migration of cells, most notably white blood cells (leukocytes). Consequently, chemokines play a central role in the development and homeostasis of the immune system, and are involved in all protective or destructive immune and inflammatory responses. Classically viewed as inducers of directed chemotactic migration, it is now clear that chemokines can stimulate a variety of other types of directed and undirected migratory behavior, such as haptotaxis, chemokinesis, and haptokinesis, in addition to inducing cell arrest or adhesion. However, chemokine receptors on leukocytes can do more than just direct migration, and these molecules can also be expressed on, and regulate the biology of, many nonleukocytic cell types. Chemokines are profoundly affected by post‐translational modification, by interaction with the extracellular matrix (ECM), and by binding to heptahelical ‘atypical’ chemokine receptors that regulate chemokine localization and abundance. This guide gives a broad overview of the chemokine and chemokine receptor families; summarizes the complex physical interactions that occur in the chemokine network; and, using specific examples, discusses general principles of chemokine function, focusing particularly on their ability to direct leukocyte migration. We provide an overview of the ~ 50 chemokines, their ~ 20 conventional receptors and the four regulatory atypical receptors. Key post‐translational modifications are summarized, as are interactions with extracellular matrix, other agonists, pathogen products, cell surface proteins and each other (curved arrows). Chemokine networks control many biological processes: we focus on their critical roles in regulating cell movement, particularly immune cell migration.