Protein tyrosine phosphatase-α complexes with the IGF-I receptor and undergoes IGF-I-stimulated tyrosine phosphorylation that mediates cell migration
| Autor: | Shirley C. Chen, Ranvikram S. Khanna, Lionel A. Samayawardhena, Darrell C. Bessette, Catherine J. Pallen |
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| Rok vydání: | 2009 |
| Předmět: |
Physiology
Protein tyrosine phosphatase Proto-Oncogene Proteins c-fyn Transfection Receptor tyrosine kinase Cell Line Receptor IGF Type 1 Fibroblast migration Dephosphorylation Mice Phosphatidylinositol 3-Kinases chemistry.chemical_compound Cell Movement Animals Insulin-Like Growth Factor I Phosphorylation Tyrosine Mice Knockout Proto-Oncogene Proteins c-yes Epidermal Growth Factor biology Receptor-Like Protein Tyrosine Phosphatases Class 4 Tyrosine phosphorylation Cell Biology Fibroblasts src-Family Kinases chemistry Biochemistry Focal Adhesion Kinase 1 Mutation biology.protein Fibroblast Growth Factor 1 Tetradecanoylphorbol Acetate Lysophospholipids Mitogen-Activated Protein Kinases Protein Processing Post-Translational Tyrosine kinase Signal Transduction |
| Zdroj: | American Journal of Physiology-Cell Physiology. 297:C133-C139 |
| ISSN: | 1522-1563 0363-6143 |
| Popis: | Protein tyrosine phosphatase-alpha (PTPalpha) is a widely expressed receptor-type phosphatase that functions in multiple signaling systems. The actions of PTPalpha can be regulated by its phosphorylation on serine and tyrosine residues, although little is known about the conditions that promote PTPalpha phosphorylation. In this study, we tested the ability of several extracellular factors to stimulate PTPalpha tyrosine phosphorylation. The growth factors IGF-I and acidic FGF induced the highest increase in PTPalpha phosphorylation at tyrosine 789, followed by PMA and lysophosphatidic acid, while EGF had little effect. Further investigation of IGF-I-induced PTPalpha tyrosine phosphorylation demonstrated that this occurs through a novel Src family kinase-independent mechanism that does not require focal adhesion kinase, phosphatidylinositol 3-kinase, or MEK. We also show that PTPalpha physically interacts with the IGF-I receptor. In contrast to IGF-I-induced PTPalpha phosphorylation, this association does not require IGF-I. The interaction of PTPalpha and the IGF-I receptor is independent of PTPalpha catalytic activity, and expression of exogenous PTPalpha does not promote IGF-I receptor tyrosine dephosphorylation, indicating that PTPalpha does not act as an IGF-I receptor phosphatase. However, PTPalpha mediates IGF-I signaling, because IGF-I-stimulated fibroblast migration was reduced by approximately 50% in cells lacking PTPalpha or in cells with mutant PTPalpha lacking the tyrosine 789 phosphorylation site. Our results suggest that PTPalpha tyrosine phosphorylation can occur in response to diverse stimuli and can be mediated by various tyrosine kinases. In the case of IGF-I, we propose that IGF-I-induced tyrosine 789 phosphorylation of PTPalpha, possibly catalyzed by the PTPalpha-associated IGF-I receptor tyrosine kinase, is required for efficient cell migration in response to this growth factor. |
| Databáze: | OpenAIRE |
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