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Papers In Press, published online ahead of print August 20, 2001
Preclinical Discovery, Human Genome Sciences, Rockville, MD 20874
Corresponding Author: paul_moore{at}hgsi.com
High-throughput cDNA sequencing has led to the identification of Interferon-
J. Biol. Chem, 10.1074/jbc.M102502200
Submitted on March 20, 2001
Revised on August 20, 2001
Accepted on August 17, 2001
Interferon-kappa, a novel type I Interferon expressed in human keratinocytes
, a novel subclass of type I Interferon that displays approximately 30% homology to other family members. Interferon- consists of 207 amino acids, including a 27-amino-acid signal peptide and a series of cysteines conserved in type I Interferons. The gene encoding Interferon- is located on the short arm of chromosome 9 adjacent to the type I Interferon gene cluster and is selectively expressed in epidermal keratinocytes. Expression of Interferon- is significantly enhanced in keratinocytes upon viral infection, upon exposure to double stranded RNA or upon treatment with either Interferon-
or Interferon-
. Administration of Interferon- recombinant protein imparts cellular protection against viral infection in a species-specific manner. Interferon- activates the ISRE signaling pathway and a panel of genes similar to those regulated by other type Interferons including anti-viral mediators and transcriptional regulators. An antibody that neutralizes the type I Interferon receptor completely blocks Interferon-k signaling, demonstrating that Interferon-k utilizes the same receptor as other type I Interferons. Interferon- therefore defines a novel subclass of type I interferon that is expressed in keratinocytes and expands the repertoire of known proteins mediating host defense.
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