Tumor progression locus 2 (Tpl-2) encodes a protein kinase involved in the progression of rodent T-cell lymphomas and in T-cell activation.
The Tpl-2 locus, cloned by provirus tagging from one of three sublines of the Moloney leukemia virus-induced rat thymoma 2769, defines a gene encoding a protein kinase associated with progression in 22.5% of the tumors. Tpl-2 is expressed primarily in spleen, thymus, liver, and lung. Provirus integration occurs in the last intron of the gene, leading to the expression of a truncated mRNA that terminates in the proviral long terminal repeat and encodes a protein with an altered C-terminal domain. Strong evidence that this genetic change confers growth advantage to affected cell clones was provided by the finding that, during cultivation of all three sublines derived from tumor 2769, cells were selected that harbored independent provirus insertions in the Tpl-2 locus. Exposure of normal rat spleen cells to Con A induces the expression of enhanced levels of Tpl-2 within the first 60 min from the time of exposure suggesting that, in normal splenocytes, Tpl-2 may be involved in the transition from a quiescent to the G1 phase of the cell cycle.
Patriotis
C
C
Fox Chase Cancer Center, Philadelphia, PA 19111.
Makris
A
A
Bear
S E
SE
Tsichlis
P N
PN
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D002478:Cells, Cultured; D003208:Concanavalin A; D015342:DNA Probes; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D008099:Liver / Q000201:enzymology; D008168:Lung / Q000201:enzymology; D008213:Lymphocyte Activation; D016399:Lymphoma, T-Cell / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D020930:MAP Kinase Kinase Kinases; D008969:Molecular Sequence Data; D008979:Moloney murine leukemia virus / Q000235:genetics; D009838:Oligodeoxyribonucleotides; D011061:Poly A / Q000235:genetics / Q000302:isolation & purification; D016133:Polymerase Chain Reaction / Q000379:methods; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D015183:Restriction Mapping; D013154:Spleen / Q000201:enzymology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D014407:Tumor Cells, Cultured
D015342:DNA Probes; D004273:DNA, Neoplasm; D009838:Oligodeoxyribonucleotides; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D003208:Concanavalin A; D011061:Poly A; D012313:RNA; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D020930:MAP Kinase Kinase Kinases; C080356:Map3k8 protein, rat