| Autor: |
Schalm SS; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA., Ballif BA, Buchanan SM, Phillips GR, Maniatis T |
| Jazyk: |
angličtina |
| Zdroj: |
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2010 Aug 03; Vol. 107 (31), pp. 13894-9. Date of Electronic Publication: 2010 Jun 25. |
| DOI: |
10.1073/pnas.1007182107 |
| Abstrakt: |
The clustered protocadherins (Pcdhs) are a large family of cadherin-like transmembrane proteins expressed in the nervous system. Stochastic expression of Pcdh genes and alternative splicing of their pre-mRNAs have the potential to generate enormous protein diversity at the cell surface of neurons. At present, the regulation and function of Pcdh proteins are largely unknown. Here, we show that Pcdhs form a heteromeric signaling complex(es), consisting of multiple Pcdh isoforms, receptor tyrosine kinases, phosphatases, and cell adhesion molecules. In particular, we find that the receptor tyrosine kinase rearranged during transformation (Ret) binds to Pcdhs in differentiated neuroblastoma cells and is required for stabilization and differentiation-induced phosphorylation of Pcdh proteins. In addition, the Ret ligand glial cell line-derived neurotrophic factor induces phosphorylation of Pcdhgamma in motor neurons and phosphorylation of Pcdhalpha and Pcdhgamma in sympathetic neurons. Conversely, Pcdh proteins are also required for the stabilization of activated Ret in neuroblastoma cells and sympathetic ganglia. Thus, Pcdhs and Ret are functional components of a phosphorylation-dependent signaling complex. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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