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cDNA cloning and characterization of a novel receptor-type protein tyrosine phosphatase expressed predominantly in
Abstract:
Protein tyrosine phosphatase has the potential to control various cellular events by negatively regulating the extent of tyrosine phosphorylation. Here, we report the isolation of a murine receptor protein tyrosine phosphatase, PTPBR7, which is expressed almost exclusively in the brain. Though the cytoplasmic portion of PTPBR7 reveals high similarity to HePTP/LC-PTP and STEP, these are, unlike PTPBR7, non-receptor protein tyrosine phosphatases. Unlike most receptor protein tyrosine phosphatases, PTPBR7 has only one cytoplasmic phosphatase domain, and its extracellular domain reveals no obvious structural similarity to known molecules. Thus, PTPBR7 defines a new subfamily of receptor-type protein tyrosine phosphatases. The putative extracellular domain of PTPBR7 was expressed in COS-7 cells as a chimeric fusion protein with an immunoglobulin Fc portion (PTPBR7-Fc). PTPBR7-Fc was secreted in the culture supernatant, confirming the capability of the extracellular domain of PTPBR7 to translocate across the cytoplasmic membrane. The cytoplasmic portion of PTPBR7 was expressed as a fusion protein in bacteria and was demonstrated to have catalytic activity. The expression of PTPBR7 was detectable in brain and especially in cerebellum but undetectable in liver, lung, heart, kidney, thymus, bone marrow, and spleen. In situ hybridization analysis revealed the most prominent signal in Purkinje cells. The predominant expression of PTPBR7 in the brain suggests that PTPBR7 may have role(s) in neuronal cells.
Insights
Researchers identified PTPBR7, a novel brain-specific receptor protein tyrosine phosphatase. This discovery defines a new phosphatase subfamily with potential roles in neuronal cells.
Area of Science:
- Molecular Biology
- Neuroscience
- Biochemistry
Background:
- Protein tyrosine phosphatases regulate cellular events by controlling tyrosine phosphorylation.
- Existing phosphatases include receptor-type and non-receptor types with varying domain structures.
Purpose of the Study:
- To report the isolation and characterization of a novel murine receptor protein tyrosine phosphatase, PTPBR7.
- To define PTPBR7's unique structural features and tissue-specific expression.
Main Methods:
- Isolation and expression of PTPBR7's extracellular and cytoplasmic domains.
- Creation of a chimeric PTPBR7-Fc fusion protein.
- Analysis of PTPBR7 expression in various tissues and cell types using in situ hybridization.
Main Results:
- PTPBR7 is a novel receptor-type protein tyrosine phosphatase with a single cytoplasmic domain and a unique extracellular domain.
- PTPBR7 is expressed almost exclusively in the brain, particularly in Purkinje cells of the cerebellum.
- The extracellular domain demonstrated translocation capability, and the cytoplasmic domain exhibited catalytic activity.
Conclusions:
- PTPBR7 represents a new subfamily of receptor-type protein tyrosine phosphatases.
- The brain-specific expression suggests a significant role for PTPBR7 in neuronal function.
- Further research is warranted to elucidate the specific functions of PTPBR7 in the nervous system.