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Research ArticleArticle

Insights into Seven and Single Transmembrane-Spanning Domain Receptors and Their Signaling Pathways in Human Natural Killer Cells

Azzam A. Maghazachi
Pharmacological Reviews September 2005, 57 (3) 339-357; DOI: https://doi.org/10.1124/pr.57.3.5
Azzam A. Maghazachi
Department of Anatomy, University of Oslo, Oslo, Norway
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Abstract

Human natural killer (NK) cells are important cells of the innate immune system. These cells perform two prominent functions: the first is recognizing and destroying virally infected cells and transformed cells; the second is secreting various cytokines that shape up the innate and adaptive immune re-sponses. For these cells to perform these activities, they express different sets of receptors. The receptors used by NK cells to extravasate into sites of injury belong to the seven transmembrane (7TM) family of receptors, which characteristically bind heterotrimeric G proteins. These receptors allow NK cells to sense the chemotactic gradients and activate second messengers, which aid NK cells in polarizing and migrating toward the sites of injured tissues. In addition, these receptors determine how and why human resting NK cells are mainly found in the bloodstream, whereas activated NK cells extravasate into inflammatory sites. Receptors for chemokines and lysophospholipids belong to the 7TM family. On the other hand, NK cells recognize invading or transformed cells through another set of receptors that belong to the single transmembrane-spanning domain family. These receptors are either inhibitory or activating. Inhibitory receptors contain the immune receptor tyrosine-based inhibitory motif, and activating receptors belong to either those that associate with adaptor molecules containing the immune receptor tyrosine-based activating motif (ITAM) or those that associate with adaptor molecules containing motifs other than ITAM. This article will describe the nature of these receptors and examine the intracellular signaling pathways induced in NK cells after ligating both types of receptors. These pathways are crucial for NK cell biology, development, and functions.

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Pharmacological Reviews: 57 (3)
Pharmacological Reviews
Vol. 57, Issue 3
1 Sep 2005
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Research ArticleArticle

Insights into Seven and Single Transmembrane-Spanning Domain Receptors and Their Signaling Pathways in Human Natural Killer Cells

Azzam A. Maghazachi
Pharmacological Reviews September 1, 2005, 57 (3) 339-357; DOI: https://doi.org/10.1124/pr.57.3.5

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Research ArticleArticle

Insights into Seven and Single Transmembrane-Spanning Domain Receptors and Their Signaling Pathways in Human Natural Killer Cells

Azzam A. Maghazachi
Pharmacological Reviews September 1, 2005, 57 (3) 339-357; DOI: https://doi.org/10.1124/pr.57.3.5
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  • Article
    • Abstract
    • I. Introduction
    • II. Signal Transduction Pathways Induced upon Ligand Binding
    • III. Cell Movement
    • IV. Natural Killer Cells Express Seven Transmembrane Chemokine Receptors
    • V. Natural Killer Cells Express Seven Transmembrane Lysophospholipid Receptors
    • VI. Single Transmembrane-Spanning Domain Receptors in Natural Killer Cells
    • VII. Sojourn of Human Natural Killer Cells into Inflammatory Sites, and Their Development
    • VIII. Concluding Remarks
    • Acknowledgments
    • Footnotes
    • References
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