Tumor Progression Locus 2 (Tpl-2) Encodes a Protein Kinase Involved in the Progression of Rodent T-Cell Lymphomas and in T-Cell Activation

• Published in: Proceedings of the National Academy of Sciences - PNAS 1993-03, Vol.90 (6), p.2251-2255
• Main Authors: Patriotis, Christos, Makris, Antonios, Bear, Susan E., Tsichlis, Philip N.
• Format: Article
• Language: English
• Subjects: activation; Amino Acid Sequence; Animal tumors. Experimental tumors; Animals; Base Sequence; Biochemistry; Biological and medical sciences; Blotting, Northern; Blotting, Southern; cDNA; Cell lines; Cells, Cultured; Complementary DNA; Concanavalin A; DNA Probes; DNA, Neoplasm - genetics; DNA, Neoplasm - isolation & purification; Experimental malignant blood diseases; gene products; genes; Genetic loci; Genomics; Liver - enzymology; Lung - enzymology; Lymphocyte Activation; lymphocytes T; Lymphoma, T-Cell - enzymology; Lymphoma, T-Cell - genetics; Lymphoma, T-Cell - physiopathology; MAP Kinase Kinase Kinases; Medical sciences; Molecular Sequence Data; Moloney murine leukemia virus - genetics; nucleotide sequence; Oligodeoxyribonucleotides; Poly A - genetics; Poly A - isolation & purification; Polymerase Chain Reaction - methods; predictions; protein kinase; Protein Kinases - genetics; Protein Kinases - metabolism; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Proteins; Proto-Oncogene Proteins; Proviruses; Rats; Rats, Inbred F344; Restriction Mapping; RNA; RNA - genetics; RNA - isolation & purification; RNA, Messenger - genetics; RNA, Messenger - metabolism; Rodents; Spleen - enzymology; Spleen - immunology; Spleen cells; T-Lymphocytes - immunology; T-Lymphocytes - physiology; Tumor cell line; Tumor Cells, Cultured; tumor progression locus 2 locus; Tumors
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.90.6.2251

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 G1phase of the cell cycle.