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Published on: March 22, 2012
Structure, expression, and activity of Tyro 3, a neural adhesion-related receptor tyrosine kinase
1Molecular Neurobiology Laboratory, Salk Institute, La Jolla, California 92037.
Abstract:
We have isolated mouse cDNA clones encoding Tyro 3, a receptor protein-tyrosine kinase (PTK) of the mammalin central nervous system (CNS). Expression of the Tyro 3 gene is strongly up-regulated in neurons of the mouse neocortex, cerebellum, and hippocampus after the day of birth, during periods of active synaptogenesis, and high expression is maintained in the adult CNS. The sequence of Tyro 3 cDNAs predicts a glycoprotein receptor with similarity to neural cell recognition and adhesion molecules--the extracellular (ligand binding) region of this receptor is composed of two immunoglobulin-related domains followed by two fibronectin type III repeats. Immunoblot and immunoprecipitation analyses with anti-Tyro 3 antibodies indicate that the 125 kD Tyro 3 protein is abundantly expressed in CNS synaptosomes, and immunohistochemical analysis of cultured hippocampal cells demonstrates that Tyro 3 is a product of neurons. Rat-2 fibroblasts stably transfected with a Tyro 3 expression construct acquire the ability to grow in soft agar, suggesting that Tyro 3 is potentially oncogenic.
Insights
Researchers identified Tyro 3, a protein-tyrosine kinase (PTK), in the mouse central nervous system (CNS). This receptor is crucial for neuron development and may play a role in cancer.
Area of Science:
- Neuroscience
- Molecular Biology
- Oncology
Background:
- Tyro 3 is a receptor protein-tyrosine kinase (PTK) found in the mammalian central nervous system (CNS).
- Its expression patterns suggest a role in neuronal development and function.
Purpose of the Study:
- To isolate and characterize mouse cDNA clones encoding the Tyro 3 receptor.
- To investigate the expression patterns and potential functions of Tyro 3 in the CNS.
- To explore the potential oncogenic properties of Tyro 3.
Main Methods:
- Isolation of mouse cDNA clones encoding Tyro 3.
- Analysis of gene expression in different brain regions and developmental stages.
- Protein expression analysis using immunoblot and immunoprecipitation.
- Immunohistochemical analysis of cultured hippocampal cells.
- Functional assays using transfected fibroblasts.
Main Results:
- Tyro 3 gene expression is upregulated in specific brain regions (neocortex, cerebellum, hippocampus) postnatally, coinciding with synaptogenesis.
- High Tyro 3 expression is maintained in the adult CNS.
- The Tyro 3 protein (125 kD) is abundant in CNS synaptosomes and is a neuronal product.
- Fibroblasts transfected with Tyro 3 gained the ability to grow in soft agar, indicating potential oncogenicity.
Conclusions:
- Tyro 3 is a glycoprotein receptor expressed in the CNS, with structural similarities to cell recognition molecules.
- Its expression profile suggests a significant role in neuronal development and function.
- Tyro 3 may possess oncogenic properties, warranting further investigation.
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