Homeostatic regulation of the immune system by receptor tyrosine kinases of the Tyro 3 family.
Receptor tyrosine kinases and their ligands mediate cell-cell communication and interaction in many organ systems, but have not been known to act in this capacity in the mature immune system. We now provide genetic evidence that three closely related receptor tyrosine kinases, Tyro 3, Axl, and Mer, play an essential immunoregulatory role. Mutant mice that lack these receptors develop a severe lymphoproliferative disorder accompanied by broad-spectrum autoimmunity. These phenotypes are cell nonautonomous with respect to lymphocytes and result from the hyperactivation of antigen-presenting cells in which the three receptors are normally expressed.
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Molecular Neurobiology Laboratory, The Salk Institute, La Jolla, CA 92037, USA.
Lemke
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D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation; D017690:Cell Transplantation; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D006706:Homeostasis; D007107:Immune System / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology; D008221:Lymphoid Tissue / Q000254:growth & development / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D009154:Mutation; D019006:Neural Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology*; D015513:Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D014176:Protein Biosynthesis; D017293:Protein S / Q000096:biosynthesis / Q000235:genetics; D011506:Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D000076202:c-Mer Tyrosine Kinase; D000094963:Axl Receptor Tyrosine Kinase; D000099255:Growth Arrest-Specific Protein 6
D036341:Intercellular Signaling Peptides and Proteins; D019006:Neural Cell Adhesion Molecules; D015513:Oncogene Proteins; D017293:Protein S; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D020794:Receptor Protein-Tyrosine Kinases; D000076202:c-Mer Tyrosine Kinase; D000094963:Axl Receptor Tyrosine Kinase; D000099255:Growth Arrest-Specific Protein 6; C490767:Mertk protein, mouse; C084944:TYRO3 protein, human; C000722290:AXL receptor tyrosine kinase, mouse