Expression of herpes simplex virus type 2 protein ICP10 PK rescues neurons from apoptosis due to serum deprivation or genetic defects.
Previous studies have shown that the herpes simplex virus type 2 protein kinase ICP10 PK activates the Ras/MEK/MAPK pathway in nonneuronal cells. Here we report that ectopically expressed ICP10 PK has anti-apoptotic activity in various paradigms of neuronal cell death. Neuronally differentiated PC12 cells and primary murine hippocampal cultures transfected with an expression vector for ICP10 PK were protected from cell death resulting from growth factor withdrawal. Protection from apoptosis was also seen in ICP10 PK-transfected hippocampal neurons from the trisomy 16 mouse, a naturally occurring genetic abnormality the human analog of which is Down syndrome. Cells transfected with an expression vector for a mutant that lacks kinase activity were not protected, although it was expressed as well as ICP10 PK. The data indicate that ICP10 PK has a broad anti-apoptotic activity in neuronal cells which depends on a functional PK.
Perkins
Dana
D
Virology/Immunology Laboratories and Department of Pharmacology and Experimental Therapeutics, University of Maryland, Baltimore, Maryland 21201, USA.
Yu
Yanxing
Y
Bambrick
Linda L
LL
Yarowsky
Paul J
PJ
Aurelian
Laure
L
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001798:Blood Proteins / Q000494:pharmacology; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000235:genetics; D015870:Gene Expression; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009154:Mutation; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016716:PC12 Cells; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D051381:Rats; D012264:Ribonucleotide Reductases / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D014162:Transfection; D014314:Trisomy; D014764:Viral Proteins / Q000096:biosynthesis*
D001798:Blood Proteins; D014764:Viral Proteins; C100671:ICP10 protein, herpes simplex virus type 2; D012264:Ribonucleotide Reductases; D017346:Protein Serine-Threonine Kinases