CO 2 /HCO 3 Modulates Receptor Protein Tyrosine Phosphatase Gamma (RPTPγ) Activity

RPTPγ is a type I tyrosine phosphatase receptor with an extracellular carbonic anhydrase‐like domain (γCAH) with 40% sequence identity to type‐α carbonic anhydrases. Carbonic anhydrases are highly efficient zinc metalloenzymes that catalyze the reversible hydration of CO 2 . However γCAH lacks two of three zinccoordinating histidine residues required for catalysis. We hypothesize that CO 2 or HCO 3 , via γCAH, modulates the tyrosine phosphatase activity of RPTPγ. We expressed full‐length, HA‐tagged human RPTPγ in Xenopus oocytes and exposed single oocytes to HEPES (balance air, pH 7.50), or 5% CO 2 /33 mM HCO 3 (balance air, pH 7.50) for 10 min, gently lysed the cell, and measured phosphatase activity using p‐nitrophenyl phosphate hydrolysis. Untreated or HEPES‐treated RPTPγ‐expressing oocytes have: (1) phosphatase activity well above that of uninjected or water‐injected controls and (2) a 300‐kDa band (detected by western blot) that is consistent with RPTPγ dimers. With RPTPγ oocytes, treatment with 5% CO 2 /33 mM HCO 3 causes: (1) a ~4‐fold increase in phosphatase activity compared to treatment with HEPES and (2) the concurrent appearance of a 160‐kDa band. These results are consistent with the hypothesis that CO 2 or HCO 3 can induce monomerization and activation of RPTPγ.