MICROINJECTED CDNA-ENCODING JAK2 PROTEIN-TYROSINE KINASE INDUCES DNA-SYNTHESIS IN NIH 3T3 CELLS

Microinjection of expression plasmids encoding either JAK2 or hyperact ive (N Delta 661)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 encodin g JAK2 was microinjected in the presence of the JAK2-selective inhibit or AG-490, whereas AG-490 did not block DNA synthesis induced by micro injected plasmid encoding (N Delta 661)rJAK2. The ability of JAK2 to i nitiate the G(o)/S cell cycle transition is comparable to that of othe r proto-oncogenes, and supports a mechanistic role for overexpressed J anus kinases in carcinogenesis. (C) 1997 Federation of European Bioche mical Societies.