Interferon-kappa, a novel type I interferon expressed in human keratinocytes.
High throughput cDNA sequencing has led to the identification of interferon-kappa, a novel subclass of type I interferon that displays approximately 30% homology to other family members. Interferon-kappa 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-kappa 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-kappa is significantly enhanced in keratinocytes upon viral infection, upon exposure to double-stranded RNA, or upon treatment with either interferon-gamma or interferon-beta. Administration of interferon-kappa recombinant protein imparts cellular protection against viral infection in a species-specific manner. Interferon-kappa activates the interferon-stimulated response element signaling pathway and a panel of genes similar to those regulated by other type I interferons including anti-viral mediators and transcriptional regulators. An antibody that neutralizes the type I interferon receptor completely blocks interferon-kappa signaling, demonstrating that interferon-kappa utilizes the same receptor as other type I interferons. Interferon-kappa therefore defines a novel subclass of type I interferon that is expressed in keratinocytes and expands the repertoire of known proteins mediating host defense.
LaFleur
D W
DW
Human Genome Sciences, 9410 Key West Ave., Rockville, MD 20850, USA.
Nardelli
B
B
Tsareva
T
T
Mather
D
D
Feng
P
P
Semenuk
M
M
Taylor
K
K
Buergin
M
M
Chinchilla
D
D
Roshke
V
V
Chen
G
G
Ruben
S M
SM
Pitha
P M
PM
Coleman
T A
TA
Moore
P A
PA
D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000378:metabolism*; D001483:Base Sequence; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9; D004305:Dose-Response Relationship, Drug; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism*; D015723:Gene Library; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis* / Q000235:genetics; D015603:Keratinocytes / Q000378:metabolism*; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000378:metabolism; D020218:Response Elements; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
D000998:Antiviral Agents; D007370:Interferon Type I; D008565:Membrane Proteins; D017471:Receptors, Interferon; C439669:interferon kappa; D053633:Receptor, Interferon alpha-beta