SHPS-1/SIRP1alpha contributes to interleukin-6 signalling.
The transmembrane glycoprotein signal regulatory protein/SHP2-substrate (SIRP1alpha/SHPS-1) has been implicated in growth factor- and cell adhesion-induced signalling. Here we report on the contribution of SIRP1alpha to IL-6 type cytokine signalling. SIRP1alpha binds the protein tyrosine phosphatase SHP2 upon treatment with interleukin-6 in a stimulation-dependent manner. Mouse embryonic fibroblasts expressing a ... SIRP1alpha protein which lacks the intracellular part show enhanced SHP2 phosphorylation and ERK1/2 activation in response to IL-6, suggesting that SIRP1alpha affects IL-6-signalling through SHP2. Whereas SHP2 phosphorylation is enhanced in SIRP1alpha-deficient cells STAT3 activation is delayed and STAT3-dependent gene induction is reduced which correlates with reduced STAT3 serine phosphorylation. Our results indicate that SIRP1alpha contributes to IL-6 signalling by counteracting SHP2 phosphorylation which consequently affects ERK-activation and STAT3-dependent transactivation as well as target gene expression. Our observations will help to understand the tight balance of MAPK- and STAT3-activation in response to IL-6 which was found to be misbalanced in many autoimmune diseases, inflammatory proliferative diseases and cancer.
Mesh Terms:
Animals, Binding Sites, Cell Line, Cytokine Receptor gp130, Enzyme Induction, Extracellular Signal-Regulated MAP Kinases, Fibroblasts, Gene Expression Regulation, Humans, Interleukin-6, Mice, Models, Biological, Phosphorylation, Phosphotyrosine, Promoter Regions, Genetic, Protein Binding, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Proto-Oncogene Proteins c-fos, Receptors, Immunologic, STAT3 Transcription Factor, Signal Transduction, Suppressor of Cytokine Signaling Proteins, Transcriptional Activation
Animals, Binding Sites, Cell Line, Cytokine Receptor gp130, Enzyme Induction, Extracellular Signal-Regulated MAP Kinases, Fibroblasts, Gene Expression Regulation, Humans, Interleukin-6, Mice, Models, Biological, Phosphorylation, Phosphotyrosine, Promoter Regions, Genetic, Protein Binding, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Proto-Oncogene Proteins c-fos, Receptors, Immunologic, STAT3 Transcription Factor, Signal Transduction, Suppressor of Cytokine Signaling Proteins, Transcriptional Activation
Cell. Signal.
Date: Jul. 01, 2008
PubMed ID: 18450421
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