Tpl-2 is an oncogenic kinase that is activated by carboxy-terminal truncation
| Autor: | Jeffrey D. Ceci, Robert M. Kovatch, Christos Patriotis, Christos Tsatsanis, Philip N. Tsichlis, Nancy A. Jenkins, Antonios M. Makris, Deborah A. Swing, Neal G. Copeland |
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| Rok vydání: | 1997 |
| Předmět: |
Molecular Sequence Data
Mice Transgenic In Vitro Techniques Protein Serine-Threonine Kinases Mitogen-activated protein kinase kinase Lymphoma T-Cell Cell Line MAP2K7 Mice Proviruses Proto-Oncogene Proteins Proto-Oncogenes Genetics Animals ASK1 Amino Acid Sequence c-Raf Kinase activity biology MAP kinase kinase kinase Cyclin-dependent kinase 2 MAP Kinase Kinase Kinases Molecular biology Introns Peptide Fragments Rats Enzyme Activation Tumor Virus Infections Calcium-Calmodulin-Dependent Protein Kinases biology.protein Cyclin-dependent kinase 9 Moloney murine leukemia virus Retroviridae Infections Developmental Biology |
| Zdroj: | Genes & Development. 11:688-700 |
| ISSN: | 1549-5477 0890-9369 |
| Popis: | Provirus insertion in the last intron of the Tpl-2 gene in retrovirus-induced rat T-cell lymphomas results in the enhanced expression of a carboxy-terminally truncated Tpl-2 kinase. Here we show that the truncated protein exhibits an approximately sevenfold higher catalytic activity and is two- to threefold more efficient in activating the MAPK and SAPK pathways relative to the wild-type protein. The truncated Tpl-2 protein and a GST fusion of the Tpl-2 carboxy-terminal tail interact when coexpressed in Sf9 cells. Their interaction down-regulates the kinase activity of the truncated protein suggesting that tail-directed intramolecular interactions regulate the Tpl-2 kinase. Tpl-2 transgenic mice expressing the wild-type protein from the proximal Lck promoter fail to show a biological phenotype, whereas mice expressing the truncated protein develop large-cell lymphoblastic lymphomas of T-cell origin. These results show that Tpl-2 is an oncogenic kinase that is activated by carboxy-terminal truncation. |
| Databáze: | OpenAIRE |
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