Interleukin (IL)-3 and granulocyte/macrophage colony-stimulating factor, but not IL-4, induce tyrosine phosphorylation, activation, and association of SHPTP2 with Grb2 and phosphatidylinositol 3'-kinase
| Autor: | M J, Welham, U, Dechert, K B, Leslie, F, Jirik, J W, Schrader |
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| Rok vydání: | 1994 |
| Předmět: |
Phosphopeptides
SH2 Domain-Containing Protein Tyrosine Phosphatases Protein Tyrosine Phosphatase Non-Receptor Type 6 Molecular Sequence Data Intracellular Signaling Peptides and Proteins Granulocyte-Macrophage Colony-Stimulating Factor Proteins Protein Tyrosine Phosphatase Non-Receptor Type 11 In Vitro Techniques Binding Competitive Mice Phosphatidylinositol 3-Kinases Phosphotransferases (Alcohol Group Acceptor) Animals Tyrosine Interleukin-3 Amino Acid Sequence Interleukin-4 Protein Tyrosine Phosphatases Peptides Phosphotyrosine Cells Cultured Adaptor Proteins Signal Transducing GRB2 Adaptor Protein |
| Zdroj: | The Journal of biological chemistry. 269(38) |
| ISSN: | 0021-9258 |
| Popis: | Binding of interleukin (IL)-3 and granulocyte/macrophage colony-stimulating factor (GM-CSF) to their high affinity cell surface receptors induces tyrosine phosphorylation of a similar set of protein substrates. We have identified one of these common substrates (p70) as the protein-tyrosine phosphatase SHPTP2. The Src homology 2 (SH2) domain of the adaptor protein Grb2 bound with high affinity to tyrosine-phosphorylated SHPTP2 following treatment of cells with IL-3 or GM-CSF, but not IL-4. This interaction was inhibited by two phosphotyrosine peptides, based on sequences within SHPTP2, which conform to the postulated consensus sequence for Grb2 SH2 recognition. Following treatment with IL-3 or GM-CSF, but not IL-4, SHPTP2 co-immunoprecipitated with antibodies directed against the p85 subunit of PI 3'-kinase. This was partially blocked by the same phosphopeptides that blocked Grb2-SH2 binding to SHPTP2. Importantly, treatment with IL-3 resulted in a 2-3-fold increase in SHPTP2 phosphatase activity. These results suggest that SHPTP2 may play an important role in integrating signals from the IL-3 and GM-CSF receptors to both Ras and PI 3'-kinase. |
| Databáze: | OpenAIRE |
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