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Altered protein tyrosine phosphorylation in scrapie-infected neuronal cell lines
Stockholm University, Faculty of Science, Department of Neurochemistry.
Manuscript (Other academic)
URN: urn:nbn:se:su:diva-23137OAI: diva2:190344
Part of urn:nbn:se:su:diva-163Available from: 2004-05-13 Created: 2004-05-13 Last updated: 2010-01-13Bibliographically approved
In thesis
1. Alterations in receptor expression and function in scrapie-infected neuronal cell lines
Open this publication in new window or tab >>Alterations in receptor expression and function in scrapie-infected neuronal cell lines
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This study shows that lipopolysaccharide (LPS) induces a robust, concentration-and time-dependent increase in nitric oxide (NO) production in the murine neuroblastoma cell line N2a by increased expression of iNOS. However, in scrapie-infected N2a cells (ScN2a), the LPS-induced NO production was completely abolished. The absence of LPS-induced NO production in ScN2a was not due to inhibited enzymatic activity of iNOS but a complete inhibition of the LPS-induced iNOS gene expression as measured by Western blot and reverse transcription-polymerase chain reaction (RT-PCR).

Furthermore, major changes in the protein tyrosine phosphorylation profile of scrapie-infected hypothalamic neurons (ScGT1-1) and ScN2a, compared to their uninfected counterparts were shown, by Western blot of whole cell extracts and of anti-phosphotyrosine immunoprecipitates, with major bands corresponding to120, 150 and 180 kD. Anti-phosphotyrosine blots of lectin-purified glycoproteins, indicated that some, but not all, of the proteins in the 120 kD band are glycosylated. Two phosphoproteins of ≈ 120 kDa were identified, the receptor tyrosine kinase, fibroblast growth factor 2 (FGFR2) and the cytoplasmic non-receptor tyrosine kinase proline-rich tyrosine kinase 2 (PYK2).

In addition, scrapie-infection induces important alterations in the expression, binding and signalling of two neurotrophic receptors, the insulin-like growth factor-1 receptor (IGF-1R) and the insulin receptor (IR) in ScN2a, as compared to uninfected N2a cells.

In ScN2a, the IGF-1R and IR protein levels were four- and two-fold increased, respectively, with an unexpected decrease in specific binding sites, as revealed by equilibrium binding studies. In the case of the IGF-1R, the apparent drop in binding sites was due to a seven-fold drop in IGF-1 affinity. Moreover, the IGF-1 stimulated IGF-1R tyrosine phosphorylation was increased in ScN2a when compared to the reduced affinity, possibly due to altered tyrosine kinase signalling in ScN2a. In the case of the IR, the binding affinity was unchanged, although insulin-stimulated IR tyrosine phosphorylation was increased.

Place, publisher, year, edition, pages
Stockholm: Institutionen för neurokemi, 2004. 116 p.
National Category
urn:nbn:se:su:diva-163 (URN)91-7265-890-8 (ISBN)
Public defence
2004-06-04, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 12 A, Stockholm, 13:00
Available from: 2004-05-13 Created: 2004-05-13Bibliographically approved

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