An Interleukin-4-Induced Transcription Factor: IL-4 Stat

• Published in: Science (American Association for the Advancement of Science) 1994-09, Vol.265 (5179), p.1701-1706
• Main Authors: Hou, Jinzhao, Schindler, Ulrike, Henzel, William J., Ho, Tze Chun, Brasseur, Mike, McKnight, Steven L.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Amino acids; B lymphocytes; Base Sequence; Biochemistry; Biological and medical sciences; Cell Line; Cell physiology; cloning; Cloning, Molecular; Cross-Linking Reagents; Crosslinking; Deoxyribonucleic acid; Dimerization; Dimers; DNA; DNA - metabolism; DNA binding proteins; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - genetics; DNA-Binding Proteins - isolation & purification; DNA-Binding Proteins - metabolism; Fundamental and applied biological sciences. Psychology; gene expression; Genes; Humans; IL-4 Stat protein; Immune response; Immune response regulation; Immunity (Disease); induction; Interleukin-4; Interleukin-4 - pharmacology; Interleukin-4 Receptor alpha Subunit; man; Messenger RNA; Models, Biological; Molecular and cellular biology; Molecular Sequence Data; Monocytes - metabolism; Phosphopeptides - metabolism; Phosphopeptides - pharmacology; Phosphorylation; Polymers; prediction; Proteins; Receptors; Receptors, Cell Surface; Receptors, Interleukin-4; Receptors, Mitogen - metabolism; Regulation; Responses to growth factors, tumor promotors, other factors; Somatic cells; STAT6 Transcription Factor; Trans-Activators - chemistry; Trans-Activators - genetics; Trans-Activators - isolation & purification; Trans-Activators - metabolism; transcription factors; Transcription Factors - chemistry; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.8085155

Interleukin-4 (IL-4) is an immunomodulatory cytokine secreted by activated T lymphocytes, basophils, and mast cells. It plays an important role in modulating the balance of T helper (Th) cell subsets, favoring expansion of the Th2 lineage relative to Th1. Imbalance of these T lymphocyte subsets has been implicated in immunological diseases including allergy, inflammation, and autoimmune disease. IL-4 may mediate its biological effects, at least in part, by activating a tyrosine-phosphorylated DNA binding protein. This protein has now been purified and its encoding gene cloned. Examination of the primary amino acid sequence of this protein indicates that it is a member of the signal transducers and activators of transcription (Stat) family of DNA binding proteins, hereby designated IL-4 Stat. Study of the inhibitory activities of phosphotyrosine-containing peptides derived from the intracellular domain of the IL-4 receptor provided evidence for direct coupling of receptor and transcription factor during the IL-4 Stat activation cycle. Such observations indicate that IL-4 Stat has the same functional domain for both receptor coupling and dimerization.