A novel gene expressed in human keratinocytes with long-term in vitro growth potential is required for cell growth

The herpes simplex virus large subunit of ribonucleotide reductase differs from its counterparts in eukaryotic and prokaryotic cells and in other viru ses in that it contains a unique domain that codes for a distinct serine-th reonine protein kinase that activates the Ras/MEK/MAPK mitogenic pathway an d is required for virus growth. Previous studies suggested that ribonucleot ide reductase protein kinase was co-opted from a cellular gene. Cellular ge nes similar to ribonucleotide reductase protein kinase were not cloned, how ever, and their function is unknown. Here we report that a novel gene (H11) that codes for a protein similar to herpes simplex virus 2 ribonucleotide reductase protein kinase, is expressed in skin tissues, cultured keratinocy tes, and the keratinocyte cell line A431. The protein is phosphorylated and it associates with the plasma membrane. H11 is expressed in keratinocytes with long-term in vitro growth potential and is coexpressed with high level s of adhesion molecules involved in signal transduction, such as beta1 inte grin. Antisense oligonucleotides that inhibit H11 expression inhibit DNA sy nthesis and keratinocyte proliferation, suggesting that H11 expression is r equired for cell growth.