PTPRO

PTPRO

PTPRO: Human Protein Tyrosine Phosphatase Receptor type O
PDB Code: 2GJT
Description
PTPRO (also known as Glomerular epithelial protein 1, GLEPP1; PTPU2) is a receptor type p rotein tyrosine phosphatase related to PTPRB-like PTPs. This phosphatase has an extended extracellular domain containing eight repeats of fibronectin type III-like motifs, a transmembrane region and a single intracellular catalytic domain and thus belongs to the R3 class of PTPs. It is primarily expressed in kidney and brain with lower expression also found in heart, placenta, spleen, colon, lymph nodes, lung and bone marrow. In mouse PTPRO mRNA is detected in the cerebral cortex, olfactory bulb and nucleus, hippocampus, motor neurons, and the spinal cord midline, dorsal root, cranial, and sympathetic ganglia and within kidney glomeruli. Multiple alternatively spliced PTPRO transcripts have been reported such as truncated PTPRO (PTPROt) which lacks the extracellular domain and is found predominantly in B lymphocytes and macrophages. Expression is developmentally regulated and it has been implicated in G0/G1 arrest.
Several functional roles have been reported for PTPRO. Studies with PTPRO -/- mice revealed that in the kidney PTPRO regulates the glomerular pressure/filtration rate through an effect on podocyte structure and function, and as a consequence the mice show a tendency to hypertension. P TPRO has also been implicated in axon growth and guidance in the developing chick motor neurons, consistent with studies in Drosophila. In monoblastoid leukaemia U937 cells PTPRO expression is induced during PMA-induced differentiation and a functional role of PTPRO in apoptosis has been suggested. In rat hepatomas, primary human lung tumors and in several human lung cancer cell lines reduced PTPRO expression levels have been detected associated with gene promoter methylation. Overexpression of PTPRO in a lung cancer cell line (A549) suppressed cell growth, delayed reentry of the cells into the cell cycle and increased susceptibility of the cells to apoptosis, consistent with a role for PTPRO as a tumour suppressor.
The protein, neuronal pentraxin with chromo domain (NPCD), has been identifed as a PTPRO-interacting protein in a yeast-two hybrid screen. Co-immunoprecipitation and pull-down approaches have confirmed the interaction and shown that at least one isoform of NPCD can serve as a substrate in vitro. Normal localization of NPCD at the plasma membrane requires PTPRO expression suggesting a possible functional role for the interaction.

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