Syndecan interacting proteins and the use thereof

Details Syndecan interacting proteins and the use thereof Syndecan interacting proteins and the use thereof

C - Chemistry, Metallurgy

12

N

C12N 15/12 (2006.01) A01K 67/027 (2006.01) A61K 31/70 (2006.01) A61K 38/17 (2006.01) A61K 48/00 (2006.01) C07K 14/47 (2006.01) C12N 15/62 (2006.01) C12Q 1/68 (2006.01) G01N 33/68 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2288376

The invention relates to the identification of a protein that binds to the cytoplasmic domain of the syndecan. This protein, now called syntenin, contains a tandem repeat of PDZ-domains that reacts with the FYA C-terminal amino acid sequence of the syndecans (Trends Biochem.Sci., 20, p. 350, 1995: Origin of PDZ {DHR, GLGF}, by M.B. Kennedy). Endogenous syntenin appears to be localized to the cytoskeleton. GFP-syntenin fusion-proteins decorate the plasma membrane and intracellular vesicles, where they co-localize and - segregate with syndecan cytoplasmic domains. Syntenin, therefore, is an unexpected candidate for connecting the cytoskeleton to heparan sulfate- assisted signal transduction pathways. The syndecan cytoplasmatic link (sycl) protein or syndecan interacting protein is referred to by the name "syntenin", meaning "putting tension on the syndecans".

L'invention concerne l'identification d'une protéine qui se fixe sur le domaine cytoplasmique du syndécane. Cette protéine, que l'on appelle maintenant synténine, contient une répétition en tandem des domaines PDZ réagissant avec la séquence FYA d'acides aminés à extrémité C terminale des syndécanes (Trends Biochem.Sci., 20, p. 350, 1995; Origine de PDZ {DHR, GLGF} par M.B. Kennedy). La synténine endogène semble se localiser sur le cytosquelette. Des protéines de fusion de synténine-GFP décorent la membrane plasmatique et les vésicules intracellulaires, dans lesquelles elles se localisent et se séparent, ensemble avec des domaines cytoplasmiques du syndécane. La synténine est, par conséquent, une candidate inespérée permettant de relier le cytosquelette à des mécanismes de transduction de signaux assistés par du sulfate d'héparane. La protéine de liaison cytoplasmique du syndécane (sycl) ou protéine interagissant avec syndécane est donc appelée "synténine", ce qui signifie "mettre la tension sur les syndécanes.

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