Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Gene Review:

Map3k8 - mitogen-activated protein kinase kinase...

Rattus norvegicus

Synonyms: D17TPL2, Mitogen-activated protein kinase kinase kinase 8, TPL-2, Tpl-2, Tpl2, ...

Patriotis, C. et al., Makris, A. et al., Patriotis, C. et al., Makris, A. et al., Belich, M.P. et al., et al.

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Disease relevance of Map3k8

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 [1].
Tumor progression locus 2 (Tpl-2) encodes a protein kinase involved in the progression of rodent T-cell lymphomas and in T-cell activation [1].
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 [1].

High impact information on Map3k8

Here we show that TPL-2 , which is homologous to MAP-kinase-kinase kinases in its catalytic domain, forms a complex with the carboxy terminus of p105 [2].
Tpl-2 is expressed primarily in spleen, thymus, liver, and lung [1].
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 [1].
In this report, we present evidence that the provirus integrated in the Tpl-2 locus in 1 of 10 T-cell lymphomas harboring a Tpl-2 rearrangement (2779) is a recombinant between MoMuLV and virus-like 30 (VL30) sequences (Mo-VL30) [3].
The Tpl-2 protein was expressed in COS-1 cells as an N-terminal fusion with a 12-amino-acid hemagglutinin tag [4].

Biological context of Map3k8

Tpl-2 is composed of eight exons and spans a 35-kb genomic DNA region [4].
The Tpl-2 proto-oncoprotein promotes cellular proliferation when overexpressed in a variety of tumor cell lines [5].
Tpl-2 induces apoptosis by promoting the assembly of protein complexes that contain caspase-9, the adapter protein Tvl-1, and procaspase-3 [5].

Other interactions of Map3k8

The proto-oncogene-encoded kinases Mos and Cot/Tpl 2 were up-regulated up to two- and four-fold, respectively, during development [6].

Analytical, diagnostic and therapeutic context of Map3k8

Immunoprecipitation of transfected COS-1 cell lysates with antihemagglutinin or anti-Tpl-2 antibodies, followed by incubation with [gamma-32P]ATP, confirmed that Tpl-2 possesses protein kinase activity [4].

References

Tumor progression locus 2 (Tpl-2) encodes a protein kinase involved in the progression of rodent T-cell lymphomas and in T-cell activation. Patriotis, C., Makris, A., Bear, S.E., Tsichlis, P.N. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
TPL-2 kinase regulates the proteolysis of the NF-kappaB-inhibitory protein NF-kappaB1 p105. Belich, M.P., Salmerón, A., Johnston, L.H., Ley, S.C. Nature (1999) [Pubmed]
Structure of a Moloney murine leukemia virus-virus-like 30 recombinant: implications for transduction of the c-Ha-ras proto-oncogene. Makris, A., Patriotis, C., Bear, S.E., Tsichlis, P.N. J. Virol. (1993) [Pubmed]
Genomic organization and expression of Tpl-2 in normal cells and Moloney murine leukemia virus-induced rat T-cell lymphomas: activation by provirus insertion. Makris, A., Patriotis, C., Bear, S.E., Tsichlis, P.N. J. Virol. (1993) [Pubmed]
Tpl-2 induces apoptosis by promoting the assembly of protein complexes that contain caspase-9, the adapter protein Tvl-1, and procaspase-3. Patriotis, C., Russeva, M.G., Lin, J.H., Srinivasula, S.M., Markova, D.Z., Tsatsanis, C., Makris, A., Alnemri, E.S., Tsichlis, P.N. J. Cell. Physiol. (2001) [Pubmed]
Expression of mitogen-activated protein kinase pathways during postnatal development of rat heart. Kim, S.O., Irwin, P., Katz, S., Pelech, S.L. J. Cell. Biochem. (1998) [Pubmed]

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