Protein-tyrosine phosphatase alpha regulates stem cell factor-dependent c-Kit activation and migration of mast cells
| Autor: | Catherine J. Pallen, Lionel A. Samayawardhena |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
GAB2
Stem cell factor Mice Transgenic Protein tyrosine phosphatase Biochemistry Models Biological Gene Expression Regulation Enzymologic Mice Phosphatidylinositol 3-Kinases FYN Cell Movement medicine Animals Mast Cells Phosphorylation cdc42 GTP-Binding Protein Molecular Biology Protein kinase B Crosses Genetic Stem Cell Factor biology Receptor-Like Protein Tyrosine Phosphatases Class 4 Mechanisms of Signal Transduction Cell Biology Mast cell Cell biology Proto-Oncogene Proteins c-kit medicine.anatomical_structure biology.protein Signal transduction Signal Transduction |
| Zdroj: | The Journal of biological chemistry. 283(43) |
| ISSN: | 0021-9258 |
| Popis: | The role of protein-tyrosine phosphatase alpha (PTPalpha) in mast cell function was investigated in tissues and cells from PTPalpha-deficient mice. Bone marrow-derived mast cells (BMMCs) lacking PTPalpha exhibit defective stem cell factor (SCF)-dependent polarization and migration. Investigation of the molecular basis for this reveals that SCF/c-Kit-stimulated activation of the Fyn tyrosine kinase is impaired in PTPalpha(-/-) BMMCs, with a consequent inhibition of site-specific c-Kit phosphorylation at tyrosines 567/569 and 719. Although c-Kit-mediated activation of phosphatidylinositol 3-kinase and Akt is unaffected, profound defects occur in the activation of downstream signaling proteins, including mitogen-activated protein kinases and Rho GTPases. Phosphorylation and interaction of Fyn effectors Gab2 and Shp2, which are linked to Rac/JNK activation in mast cells, are impaired in PTPalpha(-/-) BMMCs. Thus, PTPalpha is required for SCF-induced c-Kit and Fyn activation, and in this way regulates a Fyn-based c-Kit signaling axis (Fyn/Gab2/Shp2/Vav/PAK/Rac/JNK) that mediates mast cell migration. These defective signaling events may underlie the altered tissue-resident mast cell populations found in PTPalpha(-/-) mice. |
| Databáze: | OpenAIRE |
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