Funktion der Protein-Tyrosin-Phosphatase SHP2 bei der Interleukin 6 vermittelten Akutphase - Genregulation und T-Zell-Migration

Stimulation of the IL-6R complex leads to activation of the Jak/STAT (Januskinase/Signal Transducer and Activator of Transcription)-pathway and the Ras/Raf/MAPK-cascade. The protein tyrosine phosphatase SHP2 (SH2 - containing tyrosine phosphatase) is recruited to gp130, the signaltransducing subunit of the IL-6R-Komplex, und is an adaptor for the Ras/Raf/MAPK-cascade. Here it could be demonstrated, that SHP2 inhibits STAT-dependent gene induction, by dephosphorylating Jaks and gp130. We also tested whether the tyrosine 759 motifs in both subunits of the gp130 dimer are required for SHP2 association and tyrosine phosphorylation. Interestingly, one SHP2-recruiting phosphotyrosine motif in an single chain of the gp130 dimer is sufficient to mediate SHP2 association to the gp130 receptor subunit and its tyrosine phosphosylation as well as to attenuate IL-6-dependent gene induction. Furthermore, it was shown that repression of gene induction via tyrosine 759 does not require the presence of the SHP2 and STAT recruitment sites within the same receptor subunit, but within the same receptor complex. The tyrosine 759 motif in gp130 also attenuates gene induction mediated by the oncostatin M and leukemia inhibitory factor receptor complexes, which both contain gp130 as the shared domain. In the second part, it was shown that a T-cell line migrates chemotactically to IL-6. Probably the migration is caused by a cross talk between the IL-6 und the Integrin pathways.

Grantor dc:publisher

Publikationsserver der RWTH Aachen University

Year dc:date

2002

Author dc:creator

• Weißenbach, Manuela

Contributors dc:contributor

• Heinrich, P. C.

• info:eu-repo/classification/ddc/570
• Biowissenschaften, Biologie

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

ger

Identifier

https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-123683%22

OAI identifier oai:identifier

oai:publications.rwth-aachen.de:62089