TRANK, a novel cytokine that activates NF-kappa B and c-Jun N-terminal kinase.
We searched the expressed sequence tag database using sequence homology and identified a novel cytokine, which we have named TRANK (thioredoxin peroxidase-related activator of NF-kappa B and c-Jun N-terminal kinase). The predicted amino acid sequence of TRANK was highly homologous to that of the thiol-specific antioxidant proteins. Unlike these proteins, however, TRANK had a putative secretory signal polypeptide and was found to be secreted by cells. TRANK was expressed in most tissues and cell lines, and the gene that encodes it was mapped to chromosome Xp21-22.1. TRANK activated NF-kappa B and induced the degradation of the inhibitory subunit of NF-kappa B. In addition, TRANK up-regulated the expression of NF-kappa B-dependent gene products, ICAM-1, and inducible nitric oxide synthase. TRANK also activated c-Jun N-terminal kinase and induced the proliferation of normal human foreskin fibroblasts. Its homology with antioxidant proteins, wide distribution in tissues, and ability to activate NF-kappa B and c-Jun N-terminal kinase suggest that TRANK plays an important role in inflammation.
Haridas
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Department of Molecular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Ni
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J
Meager
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A
Su
J
J
Yu
G L
GL
Zhai
Y
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Kyaw
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Akama
K T
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Hu
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Van Eldik
L J
LJ
Aggarwal
B B
BB
D000595:Amino Acid Sequence; D000975:Antioxidants / Q000494:pharmacology; D001798:Blood Proteins / Q000737:chemistry; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D004790:Enzyme Induction / Q000187:drug effects; D006360:Heat-Shock Proteins; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D009928:Organ Specificity / Q000235:genetics; D010544:Peroxidases; D054464:Peroxiredoxins; D017386:Sequence Homology, Amino Acid
D000975:Antioxidants; D001798:Blood Proteins; D016207:Cytokines; D006360:Heat-Shock Proteins; D016328:NF-kappa B; C112841:TRANK1 protein, human; D018799:Intercellular Adhesion Molecule-1; D010544:Peroxidases; C086065:PRDX2 protein, human; D054464:Peroxiredoxins; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases