Novel mapk kinase

Details Novel mapk kinase Novel mapk kinase

C - Chemistry, Metallurgy

12

N

C12N 15/54 (2006.01) C07K 14/46 (2006.01) C07K 16/40 (2006.01) C12N 1/21 (2006.01) C12N 9/12 (2006.01) C12Q 1/48 (2006.01) G01N 33/573 (2006.01)

Patent

CA 2296070

Disclosed is a substantially pure MAPK (mitogen- activated protein kinase) kinase derived from a verte- brate, which is activated by a stimulus induced by TNF- .alpha. and/or by a stimulation of Fas antigen, and which in turn activates SAPK/JNK, but does not activate p38; and also disclosed is a DNA coding for the same. By the use of the novel MAPK kinase and the DNA coding for the same of the present invention, it has become possible to screen a novel substance having the capability to treat or prevent diseases resulting from an excess activation or inhibition of a MAP kinase cascade, and also to provide a diagnostic reagent for such diseases. In addition, the DNA of the present invention encoding the MAPK kinase can be used as a gene source for gene therapy. Further disclosed are a replicable recombin- ant DNA which comprises a replicable expression vector and, operably inserted therein, the above-mentioned DNA; a cell of a microorganism or cell culture, which is transformed with the above-mentioned replicable recombinant DNA; a polypeptide of a dominant negative form of the above-mentioned MAPK kinase and a DNA coding for the same; and an antibody capable of binding specifically to the above-mentioned MAPK kinase.

Cette invention se rapporte à une protéine kinase activée par mitogène (MAPK mitogen-activated protein kinase), sensiblement pure, issue d'un vertébré et activée par un stimulus produit par le TNF- alpha , ou un stimulus dirigé contre l'antigène Fas. Cette protéine kinase MAPK se caractérise en ce qu'elle active SAPK / JNK et non p38. L'invention se rapporte également à l'ADN codant MAPK. L'utilisation de cette kinase MAPK et de l'ADN codant cette dernière rend possible l'analyse de composés qui sont utiles au traitement ou à la prévention de maladies dans lesquelles l'activation ou l'inhibition excessive de la cascade de kinases MAPK joue un rôle, ainsi que la production de réactifs conçus pour diagnostiquer ces maladies. L'ADN codant cette kinase MAPK s'avère aussi utile en tant que source de gènes utilisés en thérapie génique. Cette invention se rapporte également à un ADN recombiné que l'on fabrique en intégrant l'ADN décrit ci-dessus à un vecteur apte à la réplication, à des micro-organismes ou cellules transformés par cet ADN recombiné apte à la réplication, à un polypeptide négatif dominant de la kinase MAPK et à un ADN codant ce polypeptide, ainsi qu'à un anticorps susceptible de se lier à la kinase MAPK.

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