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 viruses in that it contains a unique domain that codes for a distinct serine-threonine protein kinase that activates the Ras/MEK/MAPK mitogenic pathway and is required for virus growth. Previous studies suggested that ribonucleotide reductase protein kinase was co-opted from a cellular gene. Cellular genes similar to ribonucleotide reductase protein kinase were not cloned, however, 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 keratinocytes, 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 levels of adhesion molecules involved in signal transduction, such as beta1 integrin. Antisense oligonucleotides that inhibit H11 expression inhibit DNA synthesis and keratinocyte proliferation, suggesting that H11 expression is required for cell growth.
Aurelian
L
L
Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, MD 21201, USA. laurelia@umaryland.edu
Smith
C C
CC
Winchurch
R
R
Kulka
M
M
Gyotoku
T
T
Zaccaro
L
L
Chrest
F J
FJ
Burnett
J W
JW
D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D002462:Cell Membrane / Q000378:metabolism; D004247:DNA / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D018076:DNA, Complementary / Q000302:isolation & purification; D006367:HeLa Cells; D006360:Heat-Shock Proteins; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D019012:Integrin beta1 / Q000096:biosynthesis; D015603:Keratinocytes / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism*; D018832:Molecular Chaperones; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012313:RNA / Q000096:biosynthesis; D012867:Skin / Q000737:chemistry; D013997:Time Factors
D018076:DNA, Complementary; C413214:HSPB8 protein, human; D006360:Heat-Shock Proteins; D019012:Integrin beta1; D018832:Molecular Chaperones; D016376:Oligonucleotides, Antisense; D012313:RNA; D004247:DNA; D017346:Protein Serine-Threonine Kinases