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  Wnt-ligand-dependent interaction of TAK1 (TGF-beta-activated kinase-1) with the receptor tyrosine kinase Ror2 modulates canonical Wnt-signalling

Winkel, A., Stricker, S., Tylzanowski, P., Seiffart, V., Mundlos, S., Gross, G., et al. (2008). Wnt-ligand-dependent interaction of TAK1 (TGF-beta-activated kinase-1) with the receptor tyrosine kinase Ror2 modulates canonical Wnt-signalling. Cellular Signalling, 20(11), 2134-2144. doi:10.1016/j.cellsig.2008.08.009.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-7F44-9 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-7F45-7
Genre: Journal Article
Alternative Title : Cell Signal

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 Creators:
Winkel, Andreas, Author
Stricker, Sigmar1, Author              
Tylzanowski, Przemko, Author
Seiffart, Virginia, Author
Mundlos, Stefan1, Author              
Gross, Gerhard, Author
Hoffmann, Andrea, Author
Affiliations:
1Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433557              

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Free keywords: Ror2; TAK1; Wnt; PRTB; Robinow; Brachydactyly B
 Abstract: Mutations in the receptor tyrosine kinase Ror2 account for Brachydactyly type B and Robinow Syndrome. We have identified two novel factors interacting with the Ror2 intracellular domain. TAK1 (TGF-β activated kinase 1), a MAP3K, interacts with Ror2 and phosphorylates its intracellular carboxyterminal serine/thronine/proline-rich (STP) domain. This TAK1-dependent phosphorylation of Ror2 induces phosphorylation of tyrosine-residues including a MAPK-like TGY-motif. The TAK1-dependent phosphorylation is enhanced by a second cytosolic factor, PRTB, which interacts with Ror2 and with TAK1 as well. The TAK1-dependent Tyr-phosphorylation of Ror2 is not mediated by the Ror2 tyrosine kinase domain and seems predominantly triggered by cytosolic kinases. Wnt-ligand binding differentially controls the Ror2/TAK1 interaction. Wnt1-binding displaces TAK1 from Ror2 while Wnt3a and Wnt5a are unable to do so thus modifying TAK1's capacity to cause phosphorylation of Ror2. Ror2 seems to act as a Wnt co-receptor enhancing Wnt-dependent canonical pathways while Tyr- and Ser/Thr-phosphorylation of Ror2 negatively controls the efficiency of these pathways. We propose that the level of the Wnt-ligand-regulated phosphorylation by cytosolic factors determines whether Ror2 acts as a stimulator or as an inhibitor of canonical Wnt-signalling.

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 Dates: 2008-08-16
 Publication Status: Published in print
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Title: Cellular Signalling
  Alternative Title : Cell Signal
Source Genre: Journal
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Publ. Info: -
Pages: - Volume / Issue: 20 (11) Sequence Number: - Start / End Page: 2134 - 2144 Identifier: -