Involvement of SHP-2 in multiple aspects of IL-2 signaling: evidence for a positive regulatory role
| Autor: | Gadina M, Lm, Stancato, Chris Bacon, Ac, Larner, Shea Jj, O. |
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| Předmět: |
Transcriptional Activation
SH2 Domain-Containing Protein Tyrosine Phosphatases Protein Tyrosine Phosphatase Non-Receptor Type 6 Intracellular Signaling Peptides and Proteins Janus Kinase 3 Proteins Protein Tyrosine Phosphatase Non-Receptor Type 11 Protein-Tyrosine Kinases Enzyme Activation Phosphatidylinositol 3-Kinases Calcium-Calmodulin-Dependent Protein Kinases Humans Interleukin-2 Protein Tyrosine Phosphatases Cells Cultured Adaptor Proteins Signal Transducing GRB2 Adaptor Protein |
| Zdroj: | Europe PubMed Central |
| Popis: | Binding of IL-2 to its receptor activates several biochemical pathways, but precisely how these pathways are linked is incompletely understood. Here, we report that SHP-2, an SH2-domain containing tyrosine phosphatase, associates with different molecules of the IL-2 signaling cascade. Upon IL-2 stimulation, SHP-2 was coimmunoprecipitated with Grb2 and the p85 subunit of phosphatidylinositol 3-kinase. In contrast, SHP-2 was constitutively associated with JAK1 and JAK3. Finally, SHP-2 expression amplified STAT-dependent transcriptional activation whereas a dominant negative allele inhibited transactivation and the IL-2-induced activation of MAPK (mitogen-activated protein kinase). These results demonstrate the involvement of SHP-2 in multiple pathways of the IL-2 signaling cascade and provide evidence for its positive regulatory role. |
| Databáze: | OpenAIRE |
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