HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Maghazachi, A. A. Search for Related Content PubMed PubMed Citation Articles by Maghazachi, A. A.

Article

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

Department of Anatomy, University of Oslo, Oslo, Norway

Abstract

I. Introduction

A. Natural Killer Cells

B. Heterotrimeric Guanine Nucleotide-Binding (G) Proteins

C. Small G Proteins

II. Signal Transduction Pathways Induced upon Ligand Binding

A. Mitogen-Activated Protein Kinases

B. Phosphoinositide 3 Kinase

III. Cell Movement

A. Role for GTPases

B. Mechanisms Regulating Cell Motility

IV. Natural Killer Cells Express Seven Transmembrane Chemokine Receptors

A. Chemokines

B. Effects of Chemokines on Natural Killer Cell Chemotaxis

C. Mechanisms Controlling Human Natural Killer Cell Chemotaxis

V. Natural Killer Cells Express Seven Transmembrane Lysophospholipid Receptors

A. Lysophospholipids

B. Sphingosine 1-Phosphate Induces Human Natural Killer Cell Chemotaxis through G Proteins and Phosphoinositide 3 Kinase

C. Lysophophosphatidic Acid Induces Human Natural Killer Cell Chemotaxis through G Proteins

D. Effect of Lysophosphatidylcholine on Human Natural Killer Cell Chemotaxis

VI. Single Transmembrane-Spanning Domain Receptors in Natural Killer Cells

A. Overview

B. Inhibitory Natural Killer Cell Receptors

C. ITAM-Based Activating Receptors

D. Non-ITAM-Based Activating Receptors

1. NKG2D.

2. LFA-1.

3. 2B4 (CD244).

VII. Sojourn of Human Natural Killer Cells into Inflammatory Sites, and Their Development

A. Introduction

B. Natural Killer Cell Extravasation into Inflamed Sites

C. Human Natural Killer Cell Development

VIII. Concluding Remarks

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.

This article has been cited by other articles:

				B. B. Damaj, C. B. Becerra, H. J. Esber, Y. Wen, and A. A. Maghazachi Functional Expression of H4 Histamine Receptor in Human Natural Killer Cells, Monocytes, and Dendritic Cells J. Immunol., December 1, 2007; 179(11): 7907 - 7915. [Abstract] [Full Text] [PDF]