PTPσ binds and dephosphorylates neurotrophin receptors and can suppress NGF-dependent neurite outgrowth from sensory neurons
| Autor: | Jennifer Nixon, Simon S. Murray, Adam S. Wallace, Simon Lee, Andrew W. Stoker, Clare Faux, Muhamed Hawadle |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
animal structures
Neurite Cell Survival Receptors Nerve Growth Factor Protein tyrosine phosphatase Tropomyosin receptor kinase A Axonogenesis Receptor tyrosine kinase Cell Line Dephosphorylation 03 medical and health sciences 0302 clinical medicine Receptor protein tyrosine phosphatase σ Ganglia Spinal Protein Interaction Mapping Neurites Animals Humans Immunoprecipitation Receptor trkB Receptor trkC Nerve Growth Factors Neurons Afferent Phosphorylation Receptor trkA Molecular Biology Cells Cultured 030304 developmental biology 0303 health sciences biology Neurite outgrowth Receptor-Like Protein Tyrosine Phosphatases Class 2 Cell Biology Trk receptor tyrosine kinase Protein Structure Tertiary Rats Cell biology nervous system Receptor-Like Protein Tyrosine Phosphatases Trk receptor embryonic structures biology.protein Neurotrophin Chickens 030217 neurology & neurosurgery Protein Binding |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1773:1689-1700 |
| ISSN: | 0167-4889 |
| Popis: | Neurotrophin receptors of the Trk family play a vital role in the survival of developing neurons and the process of axonogenesis. The Trk family are receptor protein tyrosine kinases (RTKs) and their signalling in response to neurotrophins is critically dependent upon their ability to transphosphorylate and act as signalling centres for multiple adaptor proteins and distinct, downstream pathways. Such phosphotyrosine signalling also depends upon the appropriate counter-regulation by phosphatases. A large family of receptor-like protein tyrosine phosphatases (RPTPs) are also expressed in developing neurons and in this study we have examined the ability of the phosphatase PTPsigma to interact with and regulate Trk proteins in transfected HEK 293T cells. PTPsigma can bind differentially to Trk proteins, binding stably in complexes with TrkA and TrkC, but not TrkB. The transmembrane domains of PTPsigma and TrkA appear to be sufficient for the direct or indirect interaction between these two receptors. Furthermore, PTPsigma is shown to dephosphorylate all three Trk receptors and suppress their phosphorylation in the presence of neurotrophins. In addition, overexpression of PTPsigma in primary sensory neurons in culture inhibits neurite outgrowth without affecting the short-term survival of these neurons. PTPsigma can thus show differential complex formation with different Trk family members and in neurons can selectively target the neurite-forming signalling pathway driven by TrkA. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect