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Protein tyrosine phosphatase receptor type J (PTPRJ)
- Target
- PTPRJ
- Molecular classification
- Enzyme, Receptor, R3 subfamily of receptor protein tyrosine phosphatases (RPTPs)
01
Overview
Protein tyrosine phosphatase receptor type J (PTPRJ) is a receptor-type protein tyrosine phosphatase that dephosphorylates key signaling molecules including receptor tyrosine kinases, JAK2, and Eph receptors. It functions as a negative regulator of various signal transduction pathways affecting cell proliferation, differentiation, metabolism, and bone maturation. PTPRJ is downregulated in several epithelial cancers and thought to act as an antioncogene. It also inhibits leptin and insulin signaling, implicating it in metabolic disease. Therapeutic targeting of PTPRJ is challenged by enzyme active site conservation and cell permeability issues, but it remains a compelling but underexploited drug target for oncology and metabolic indications.
- Other names
- DEP-1HPTPηCD148
02
Mechanism of action
Inhibition of phosphatase activity to modulate aberrant tyrosine signaling; Potential negative regulation of oncogenic kinases and metabolic signaling by preventing dephosphorylation
03
Biological functions
Signal transductionNegative regulation of phosphorylation of tyrosine kinasesRegulation of cell proliferationRegulation of cell differentiationModulation of metabolism (insulin and leptin signaling)Regulation of osteoclastogenesis and bone resorption
04
Disease associations
Cancer (acts as an antioncogene; downregulated in several epithelial tumors)Metabolic disease (diabetes, obesity: regulates insulin and leptin signaling)Neurodegenerative disease (suggested by regulation of neuronal proteins)Bone disorders (possibly due to its role in osteoclast maturation)
05
Safety considerations
Selectivity (closely related PTP family members have highly conserved active sites, making off-target effects possible)Potential for immunological and metabolic disruption if physiological negative regulation is antagonizedDifficulty in developing bioavailable and cell-penetrant inhibitors
06
Interacting drugs
No approved drugs directly targeting PTPRJ as of August 2025
3 more in the full profile.
07
Biomarkers
Protein expression levels (for certain cancers, PTPRJ is commonly downregulated)Expression or phosphorylation status (for patient selection or efficacy monitoring, especially for cancer and metabolic therapies targeting the pathway)
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