Abstract
The leukemia inhibitory factor receptor (LIF-R) subunit is a component of cell-surface receptor complexes for the multifunctional cytokines, LIF, cardiotrophin-1, ciliary neurotrophic factor, and human oncostatin M. The structure of the human LIF-R gene is similar to that of the mouse gene. The transmembrane receptor is encoded by 19 exons. Two distinct 5' non-coding exons are present, indicating the existence of alternative promoters. An extra-exon specific to the mouse soluble receptor contains a stop codon and polyadenylation signals in a B2 repetitive element. On the other hand, LIF-R mRNAs containing unspliced introns are abundantly present in human tissues. These intronic sequences introduce a termination codon before the transmembrane domain. Human choriocarcinoma cells expressing these mRNAs release soluble LIF-R. The cytoplasmic domain of LIF-R can generate the signals for growth arrest and differentiation of mouse myeloid leukemic cells when they are induced to form a homodimer of the cytoplasmic domain independently of gp130. Two membrane-distal tyrosines on the YXXQ motif of LIF-R are critical not only for STAT3 activation but also for growth arrest and macrophage differentiation of WEHI-3B D+ cells.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Amino Acid Motifs
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Animals
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Cell Differentiation
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DNA-Binding Proteins / physiology
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Dimerization
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Embryonal Carcinoma Stem Cells
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Female
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Gene Expression Regulation
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Genes
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Growth Inhibitors / physiology
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Humans
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Interleukin-6*
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Leukemia Inhibitory Factor
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Leukemia Inhibitory Factor Receptor alpha Subunit
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Leukemia, Myeloid / pathology
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Lymphokines / physiology
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Mice
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Neoplasm Proteins / genetics
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Neoplasm Proteins / physiology
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Neoplastic Stem Cells / metabolism
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Neoplastic Stem Cells / pathology
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Pregnancy
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Protein Structure, Tertiary
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RNA, Messenger / metabolism
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RNA, Neoplasm / metabolism
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Receptors, Cytokine / chemistry
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Receptors, Cytokine / genetics
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Receptors, Cytokine / physiology*
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Receptors, OSM-LIF
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STAT3 Transcription Factor
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Sequence Homology, Nucleic Acid
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Solubility
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Species Specificity
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Structure-Activity Relationship
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Trans-Activators / physiology
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Tumor Cells, Cultured
Substances
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DNA-Binding Proteins
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Growth Inhibitors
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Interleukin-6
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LIF protein, human
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LIFR protein, human
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Leukemia Inhibitory Factor
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Leukemia Inhibitory Factor Receptor alpha Subunit
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Lif protein, mouse
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Lifr protein, mouse
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Lymphokines
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Neoplasm Proteins
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RNA, Messenger
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RNA, Neoplasm
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Receptors, Cytokine
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Receptors, OSM-LIF
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STAT3 Transcription Factor
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STAT3 protein, human
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Stat3 protein, mouse
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Trans-Activators