PSTPIP is a substrate of PTP-PEST and serves as a scaffold guiding PTP-PEST toward a specific dephosphorylation of WASP
| Autor: | Jean-François Côté, Laurence A. Lasky, Maxime Hallé, Susan D. Spencer, Ping Lin Chung, Jean-François Théberge, Michel L. Tremblay |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Scaffold protein
Blotting Western Protein Tyrosine Phosphatase Non-Receptor Type 12 macromolecular substances Biology Transfection environment and public health Biochemistry Cell Line Oncogene Protein pp60(v-src) src Homology Domains chemistry.chemical_compound Mice Epidermal growth factor Animals Tyrosine Phosphorylation Molecular Biology Adaptor Proteins Signal Transducing Glutathione Transferase Binding Sites Kinase fungi Proteins Tyrosine phosphorylation Cell Biology 3T3 Cells Fibroblasts Precipitin Tests Actins Cell biology Protein Structure Tertiary enzymes and coenzymes (carbohydrates) Cytoskeletal Proteins chemistry Microscopy Fluorescence COS Cells Chromatography Thin Layer Protein Tyrosine Phosphatases Carrier Proteins Tyrosine kinase Wiskott-Aldrich Syndrome Protein Proto-oncogene tyrosine-protein kinase Src Plasmids Protein Binding |
| Zdroj: | The Journal of biological chemistry. 277(4) |
| ISSN: | 0021-9258 |
| Popis: | PSTPIP is a tyrosine-phosphorylated protein involved in the organization of the cytoskeleton. Its ectopic expression induces filipodial-like membrane extensions in NIH 3T3 cells. We previously observed a defect in cytokinesis and an increase in the tyrosine phosphorylation of PSTPIP in PTP-PEST-deficient fibroblasts. In this article, we demonstrate that PTP-PEST and PSTPIP are found in the same complexes in vivo and that they interact directly through the CTH domain of PTP-PEST and the coiled-coil domain of PSTPIP. We tested pathways that could regulate the tyrosine phosphorylation of PSTPIP. We found that the activation of the epidermal growth factor and platelet-derived growth factor receptors can induce PSTPIP phosphorylation. With the use of the PP2 inhibitor, we demonstrate that Src kinases are not involved in the epidermal growth factor-mediated phosphorylation of PSTPIP. Together with previous results, this suggests that c-Abl is the critical tyrosine kinase downstream of growth factor receptors responsible for PSTPIP phosphorylation. We also demonstrate that PTP-PEST dephosphorylates PSTPIP at tyrosine 344. Importantly, we identified tyrosine 344 as the main phosphorylation site of PSTPIP by performing tryptic phosphopeptide maps. This is an important finding since tyrosine 367 of PSTPIP was also proposed as a candidate phosphorylation site involved in the negative regulation of the association between PSTPIP and WASP. In this respect, we observed that the PSTPIP·WASP complex is stable in vivo and is not affected by the phosphorylation of PSTPIP. Furthermore, we demonstrate that PSTPIP serves as a scaffold protein between PTP-PEST and WASP and allows PTP-PEST to dephosphorylate WASP. This finding suggests a possible mechanism for PTP-PEST to directly modulate actin remodeling through the PSTPIP-WASP interaction. |
| Databáze: | OpenAIRE |
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