WFRF:(Simi S)
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| Fältnamn | Indikatorer | Metadata |
|---|---|---|
| 000 | 02801naa a2200409 4500 | |
| 001 | oai:prod.swepub.kib.ki.se:119311442 | |
| 003 | SwePub | |
| 008 | 240701s2009 | |||||||||||000 ||eng| | |
| 024 | 7 | a http://kipublications.ki.se/Default.aspx?queryparsed=id:1193114422 URI |
| 024 | 7 | a https://doi.org/10.1242/jcs.0550612 DOI |
| 040 | a (SwePub)ki | |
| 041 | a engb eng | |
| 042 | 9 SwePub | |
| 072 | 7 | a ref2 swepub-contenttype |
| 072 | 7 | a art2 swepub-publicationtype |
| 100 | 1 | a Vilar, M4 aut |
| 245 | 1 0 | a Ligand-independent signaling by disulfide-crosslinked dimers of the p75 neurotrophin receptor |
| 264 | 1 | b The Company of Biologists,c 2009 |
| 520 | a Dimerization is recognized as a crucial step in the activation of many plasma membrane receptors. However, a growing number of receptors pre-exist as dimers in the absence of ligand, indicating that, although necessary, dimerization is not always sufficient for signaling. The p75 neurotrophin receptor (p75NTR) forms disulfide-linked dimers at the cell surface independently of ligand binding through Cys257 in its transmembrane domain. Here, we show that crosslinking of p75NTR dimers by cysteine-scanning mutagenesis results in constitutive, ligand-independent activity in several pathways that are normally engaged upon neurotrophin stimulation of native receptors. The activity profiles of different disulfide-crosslinked p75NTR mutants were similar but not identical, suggesting that different configurations of p75NTR dimers might be endowed with different functions. Interestingly, crosslinked p75NTR mutants did not mimic the effects of the myelin inhibitors Nogo or MAG, suggesting the existence of ligand-specific activation mechanisms. Together, these results support a conformational model of p75NTR activation by neurotrophins, and reveal a genetic approach to generate gain-of-function receptor variants with distinct functional profiles. | |
| 700 | 1 | a Charalampopoulos, I4 aut |
| 700 | 1 | a Kenchappa, RS4 aut |
| 700 | 1 | a Reversi, A4 aut |
| 700 | 1 | a Klos-Applequist, JM4 aut |
| 700 | 1 | a Karaca, Eu Karolinska Institutet4 aut |
| 700 | 1 | a Simi, Au Karolinska Institutet4 aut |
| 700 | 1 | a Spuch, C4 aut |
| 700 | 1 | a Choi, S4 aut |
| 700 | 1 | a Friedman, WJ4 aut |
| 700 | 1 | a Ericson, J4 aut |
| 700 | 1 | a Schiavo, G4 aut |
| 700 | 1 | a Carter, BD4 aut |
| 700 | 1 | a Ibanez, CFu Karolinska Institutet4 aut |
| 710 | 2 | a Karolinska Institutet4 org |
| 773 | 0 | t Journal of cell scienced : The Company of Biologistsg 122:18Pt 18, s. 3351-3357q 122:18Pt 18<3351-3357x 1477-9137x 0021-9533 |
| 856 | 4 | u http://jcs.biologists.org/content/joces/122/18/3351.full.pdf |
| 856 | 4 8 | u http://kipublications.ki.se/Default.aspx?queryparsed=id:119311442 |
| 856 | 4 8 | u https://doi.org/10.1242/jcs.055061 |
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