ICAM-2 redistributed by ezrin as a target for killer cells

VERY little is known about the receptors and target molecules involved in natural killer (NK) cell activity. Here we present a model system in which interleukin-2-activated killing by NK cells depends on the intercellular adhesion molecule ICAM-2 and is regulated by the distribution of ICAM-2. The l...

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Published in:Nature (London) 1996-07, Vol.382 (6588), p.265-268
Main Authors: Helander, Tuula S, Carpén, Olli, Turunen, Ossi, Kovanen, Panu E, Vaheri, Antti, Timonen, Tuomo
Format: Article
Language:English
Subjects:
Adhesion
Animals
Antigens, CD - metabolism
Antigens, CD - physiology
Biological and medical sciences
Cell Adhesion Molecules - metabolism
Cell Adhesion Molecules - physiology
Cell Line
Cellular biology
Chromosomes, Human, Pair 6
Cytoskeletal Proteins - metabolism
Cytotoxicity, Immunologic
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Humanities and Social Sciences
Humans
Hybrid Cells
Immunobiology
Interleukin-2 - physiology
Killer Cells, Natural - immunology
letter
Lymphocyte Activation - physiology
Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation
Mice
multidisciplinary
Pathology
Phosphoproteins - genetics
Phosphoproteins - metabolism
Proteins
Science
Science (multidisciplinary)
Transfection
Tumor Cells, Cultured
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description VERY little is known about the receptors and target molecules involved in natural killer (NK) cell activity. Here we present a model system in which interleukin-2-activated killing by NK cells depends on the intercellular adhesion molecule ICAM-2 and is regulated by the distribution of ICAM-2. The level of ICAM-2 expression in NK-sensitive and resistant cells is similar, but in sensitive cells ICAM-2 is concentrated into bud-like cellular projections known as uropods, whereas in resistant cells it is evenly distributed. The cytoskeletal–membrane linker protein ezrin is also localized in uropods. Transfection of human ezrin into NK-resistant cells induces uropod formation, redistribution of ICAM-2 and ezrin, and sensitizes target cells to interleukin-2-activated killing. These results reveal a new mechanism of target-cell recognition: cytotoxic cells recognize adhesion molecules that are already present on normal cells, but in diseased cells are concentrated into a biologically active cell-surface region by cytoskeletal reorganization. The results also highlight the importance of cytoskeletal interactions in the regulation of ICAM-2-mediated adhesive phenomena.
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subjects Adhesion
Animals
Antigens, CD - metabolism
Antigens, CD - physiology
Biological and medical sciences
Cell Adhesion Molecules - metabolism
Cell Adhesion Molecules - physiology
Cell Line
Cellular biology
Chromosomes, Human, Pair 6
Cytoskeletal Proteins - metabolism
Cytotoxicity, Immunologic
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Humanities and Social Sciences
Humans
Hybrid Cells
Immunobiology
Interleukin-2 - physiology
Killer Cells, Natural - immunology
letter
Lymphocyte Activation - physiology
Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation
Mice
multidisciplinary
Pathology
Phosphoproteins - genetics
Phosphoproteins - metabolism
Proteins
Science
Science (multidisciplinary)
Transfection
Tumor Cells, Cultured
title ICAM-2 redistributed by ezrin as a target for killer cells
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