Identification and characterization of a transmembrane isoform of CD160 (CD160-TM), a unique activating receptor selectively expressed upon human NK cell activation.
CD160 has been initially identified as a GPI-anchored MHC-class I activating receptor mainly expressed on peripheral blood NK cells. Herein, we report the identification of three additional CD160-related mRNAs generated through alternative splicings of the CD160 gene, among which one encoded a putative CD160 transmembrane isoform (CD160-TM). We first establish that CD160-TM surface expression is highly restricted to NK cells and is activation-dependent. Additionally, we provide evidence that CD160-TM represents a novel activating receptor, as assessed by the increased CD107a NK cell surface mobilization observed upon its engagement. Finally, we demonstrate that the CD160-TM cytoplasmic tail is by itself sufficient to mediate the recruitment of Erk1/2 signaling pathway, and that the initiation of this activation process is dependent on the Src-family kinase p56(lck). The identification of CD160-TM therefore provides new possibilities regarding the role of CD160 isoforms in the regulation of NK cell functions.
Giustiniani
Jérôme
J
Institeut National de la Santé et de la Recherche Médicale Unite 841, Department of Immunology, Université Paris 12, Faculté de Médecine de Créteil, Créteil, France.
Bensussan
Armand
A
Marie-Cardine
Anne
A
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification* / Q000502:physiology; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D045744:Cell Line, Tumor; D002999:Clone Cells; D058851:GPI-Linked Proteins; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D019169:Jurkat Cells; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification* / Q000502:physiology*; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology; D012333:RNA, Messenger / Q000302:isolation & purification; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification* / Q000502:physiology; D016192:Resting Phase, Cell Cycle / Q000235:genetics / Q000276:immunology
D015703:Antigens, CD; C114505:CD160 protein, human; D058851:GPI-Linked Proteins; D008565:Membrane Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D011971:Receptors, Immunologic