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Killer Activation Receptors (KARs) are receptors expressed on the plasmatic membrane of Natural Killer cells (NK cells). KARs work with inhibitory Killer-cell immunoglobulin-like receptors (KIRs), which inactivate them in order to regulate the NK cells functions on hosted or transformed cells. These two kinds of specific receptors have some morphological features in common, such as being transmembrane proteins. The similarities are specially found in the extracellular domains and, therefore, the differences tend to be in the intracellular domains. KARs and KIRs can only do their function in presence of ''immunoreceptors'' that contain tyrosine and have an activator or inhibitor function (they are called ITAMs and ITIMs). At first, it was thought that there were only one KAR and one KIR (two-receptor model). In the last decade, lots of different KARs and KIRs, such as ''NKp46'' or NKG2D, have been discovered (opposing-signals model). == Morphology == There are two different kinds of surface receptors which are responsible for triggering NK-mediated natural cytotoxicity: the NK KARs (meaning: Killer Activation Receptors) and the NK KIRs (meaning: Killer Inhibitory Receptors). Such receptors have a broad binding specificity and, therefore, are able to broadcast opposite signals. It is the balance between these competing signals that determines whether or not the cytotoxic activity of the NK cell should get started. As KARs and KIRs are receptors with antagonic effects on NK cells, they have some structural characteristics in common. Firstly, both of them are usually transmembrane proteins. Apart from that, the extracellular domains of these proteins tend to have similar molecular features and are responsible for ligand recognition. Therefore, the opposing functions these receptors have must be attributed to differences in their intracellular domains. KARs proteins possess positively charged transmembrane residues and short cytoplasmic tails that contain few intracellular signaling domains. In contrast, KIRs proteins usually have long cytoplasmic tails. As the chains which form KARs are not able to mediate any signal transduction in isolation, a common feature of such receptors is the presence of noncovalently linked subunits that contain immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic tails. ITAMs are composed of a conserved sequence of amino acids, including two Tyr-x-x-Leu/Ile elements (where x is any amino acid) separated by six to eight amino acid residues. When the binding of an activation ligand to an activation receptor complex occurs, the tyrosine residues in the ITAMs in the associated chain are phosphorylated by kinases, and a signal that promotes natural cytotoxicity is conveyed to the interior of the NK cell. Therefore, ITAMs are involved in the facilitation of signal transduction. These subunits are moreover composed of an accessory signaling molecule such as ''CD3ζ'', the γc chain, or one of two adaptor proteins called ''DAP10'' and ''DAP12''. All of these molecules possess negatively charged transmembrane domains. A common feature of members of all KIR is the presence of immunoreceptor tyrosine-based inhibition motifs (ITIMs) in their cytoplasmic tails. ITIMs are composed of the sequence Ile/Val/Leu/Ser-x-Tyr-x-x-Leu/Val, where x denotes any amino acid. The latter are essential to the signaling functions of these molecules. When an inhibitory receptor is stimulated by the binding of MHC class I, kinases and phosphatases are recruited to the receptor complex. This is how ITIMs counteract the effect of kinases initiated by activating receptors and manage to inhibit the signal transduction within the NK cell. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Killer activation receptor」の詳細全文を読む スポンサード リンク
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