Microinjected cDNA encoding JAK2 protein-tyrosine kinase induces DNA synthesis in NIH 3T3 cells.
Microinjection of expression plasmids encoding either JAK2 or hyperactive (Ndelta661)rJAK2 into serum-starved NIH 3T3 cells resulted in 20-30-fold induction of DNA synthesis. Control microinjections of buffer or parental pcDNA3 vector resulted in only 3-5-fold induction of DNA synthesis. Induction of DNA synthesis was blocked when plasmid encoding JAK2 was microinjected in the presence of the JAK2-selective inhibitor AG-490, whereas AG-490 did not block DNA synthesis induced by microinjected plasmid encoding (Ndelta661)rJAK2. The ability of JAK2 to initiate the G(o)/S cell cycle transition is comparable to that of other proto-oncogenes, and supports a mechanistic role for overexpressed Janus kinases in carcinogenesis.
Smith
M R
MR
Intramural Research Support Program, Science Applications International Corporation Frederick, National Cancer Institute - Frederick Cancer Research and Development Center, MD 21702-1201, USA.
Duhe
R J
RJ
Liu
Y
Y
Farrar
W L
WL
D016475:3T3 Cells; D000818:Animals; D004247:DNA / Q000096:biosynthesis*; D004261:DNA Replication / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D053614:Janus Kinase 2; D007700:Kinetics; D051379:Mice; D008845:Microinjections / Q000379:methods; D009570:Nitriles / Q000494:pharmacology; D010957:Plasmids; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism; D014162:Transfection / Q000379:methods; D020032:Tyrphostins
D004791:Enzyme Inhibitors; D009570:Nitriles; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D004247:DNA; D011505:Protein-Tyrosine Kinases; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2