Induction of the Ly-6A/E gene by interferon alpha/beta and gamma requires a DNA element to which a tyrosine-phosphorylated 91-kDa protein binds.
The murine Ly-6A/E gene is transcriptionally induced in cells exposed to interferon alpha/beta or gamma (IFN-alpha/beta or IFN-gamma). Analysis of the 5' flanking sequence using reporter plasmids that contain upstream elements of the Ly-6E gene has previously identified an approximately 850-base-pair IFN-responsive region that lacked an IFN-alpha-stimulated response element (ISRE), the element present and required for an IFN-alpha response of a number of genes. Analysis by deletion and stable transfection of the IFN-responsive region of the Ly-6E promoter has defined an 80-base-pair region containing an IFN-gamma activation site (GAS) but no ISRE that allows IFN-gamma and IFN-alpha inducibility of the Ly-6E gene. As tested by specific antiserum, a 91-kDa protein known to be activated in IFN-alpha- or IFN-gamma-treated cells binds to the GAS element from the Ly-6E promoter. The 91-kDa protein exists as an inactive cytoplasmic precursor and depends on tyrosine phosphorylation for its activation. Thus the same 91-kDa protein appears to act in the signal transduction pathways of both types of IFN for the Ly-6-A/E gene.
Khan
K D
KD
Section of Immunobiology, Yale University Medical School, New Haven, CT 06510.
Shuai
K
K
Lindwall
G
G
Maher
S E
SE
Darnell
J E
JE
Bothwell
A L
AL
D000818:Animals; D000950:Antigens, Ly / Q000096:biosynthesis*; D001483:Base Sequence; D003513:Cycloheximide / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D016898:Interferon-alpha / Q000494:pharmacology; D016899:Interferon-beta / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007372:Interferons / Q000494:pharmacology*; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis
D000950:Antigens, Ly; D004268:DNA-Binding Proteins; D016898:Interferon-alpha; D012333:RNA, Messenger; D016899:Interferon-beta; D007371:Interferon-gamma; D007372:Interferons; D003513:Cycloheximide; D011505:Protein-Tyrosine Kinases