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Receptor protein tyrosine phosphatase alpha activates pp60c-src and is involved in neuronal differentiation
J den Hertog1, C E Pals, M P Peppelenbosch
1Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Utrecht.
Abstract:
Here we report that protein tyrosine phosphatases (PTPases), like their enzymatic counterpart the protein tyrosine kinases, can play an important role in cell differentiation. Expression of the transmembrane PTPase receptor protein tyrosine phosphatase alpha (RPTP alpha) is transiently enhanced during neuronal differentiation of embryonal carcinoma (EC) and neuroblastoma cells. Retinoic acid induces wild type P19 cells to differentiate into endoderm- and mesoderm-like cells. By contrast, retinoic acid treatment leads to neuronal differentiation of P19 cells, ectopically expressing functional RPTP alpha, as illustrated by their ability to generate action potentials. Endogenous pp60c-src kinase activity is enhanced in the RPTP alpha-transfected cells, which may be due to direct dephosphorylation of the regulatory Tyr residue at position 527 in pp60c-src by RPTP alpha. Our results demonstrate that RPTP alpha is involved in neuronal differentiation and imply a role for pp60c-src in the differentiation process.
Insights
Protein tyrosine phosphatases (PTPases) are crucial for cell differentiation. Receptor protein tyrosine phosphatase alpha (RPTP alpha) expression enhances neuronal differentiation, potentially via pp60c-src kinase.
Area of Science:
- Molecular Biology
- Cell Biology
- Neuroscience
Background:
- Protein tyrosine phosphatases (PTPases) are enzymes involved in cell signaling.
- Their role in cell differentiation, particularly neuronal differentiation, is an area of active research.
- Receptor-like PTPases (RPTPs) are transmembrane proteins with extracellular domains.
Purpose of the Study:
- To investigate the role of receptor protein tyrosine phosphatase alpha (RPTP alpha) in cell differentiation.
- To determine if RPTP alpha influences neuronal differentiation in specific cell types.
- To explore the relationship between RPTP alpha and pp60c-src kinase activity during differentiation.
Main Methods:
- Studying the expression of RPTP alpha during neuronal differentiation of embryonal carcinoma (EC) and neuroblastoma cells.
- Utilizing retinoic acid to induce differentiation in P19 cells.
- Ectopically expressing functional RPTP alpha in P19 cells and assessing neuronal differentiation markers.
- Measuring endogenous pp60c-src kinase activity in RPTP alpha-transfected cells.
Main Results:
- RPTP alpha expression is transiently increased during neuronal differentiation of EC and neuroblastoma cells.
- Retinoic acid induces neuronal differentiation in P19 cells engineered to express RPTP alpha.
- RPTP alpha expression correlates with enhanced pp60c-src kinase activity.
- RPTP alpha may dephosphorylate Tyr527 in pp60c-src, activating the kinase.
Conclusions:
- RPTP alpha plays a significant role in promoting neuronal differentiation.
- The study suggests a functional link between RPTP alpha and pp60c-src in the context of cell differentiation.
- These findings highlight PTPases as important regulators of neuronal development.