An interleukin-4-induced transcription factor: IL-4 Stat.
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.
Hou
J
J
Tularik, Inc., South San Francisco, CA 94080.
Schindler
U
U
Henzel
W J
WJ
Ho
T C
TC
Brasseur
M
M
McKnight
S L
SL
D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D003432:Cross-Linking Reagents; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D053662:Interleukin-4 Receptor alpha Subunit; D008954:Models, Biological; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism; D010748:Phosphopeptides / Q000378:metabolism / Q000494:pharmacology; D010766:Phosphorylation; D011108:Polymers; D011956:Receptors, Cell Surface; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen / Q000378:metabolism*; D050800:STAT6 Transcription Factor; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D003432:Cross-Linking Reagents; D004268:DNA-Binding Proteins; C504000:IL4R protein, human; D053662:Interleukin-4 Receptor alpha Subunit; D010748:Phosphopeptides; D011108:Polymers; D011956:Receptors, Cell Surface; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D015847:Interleukin-4; D004247:DNA