Identification of novel splicing variants of protein tyrosine phosphatase receptor type Z.

Protein tyrosine phosphatase receptor type Z (PTPRZ, also known as PTPζ or RPTPβ) is preferentially expressed in the central nervous system (CNS). PTPRZ plays important roles during development and adulthood in CNS myelination, learning and memory. Three splicing isoforms for PTPRZ have been identified to date: two receptor type isoforms, PTPRZ-A and PTPRZ-B, and one secretory isoform, PTPRZ-S.

Consensus substrate sequence for protein-tyrosine phosphatase receptor type Z.

Protein-tyrosine phosphatase receptor type Z (Ptprz) has multiple substrate proteins, including G protein-coupled receptor kinase-interactor 1 (Git1), membrane-associated guanylate kinase, WW and PDZ domain-containing 1 (Magi1), and GTPase-activating protein for Rho GTPase (p190RhoGAP). We have identified a dephosphorylation site at Tyr-1105 of p190RhoGAP; however, the structural determinants employed for substrate recognition of Ptprz have not been fully defined. In the present study, we revealed that Ptprz selectively dephosphorylates Git1 at Tyr-554, and Magi1 at Tyr-373 and Tyr-858 by in vitro and cell-based assays.

Metalloproteinase- and gamma-secretase-mediated cleavage of protein-tyrosine phosphatase receptor type Z.

Protein-tyrosine phosphatase receptor type Z (Ptprz) is preferentially expressed in the brain as a major chondroitin sulfate proteoglycan. Three splicing variants, two receptor isoforms and one secretory isoform, are known. Here, we show that the extracellular region of the receptor isoforms of Ptprz are cleaved by metalloproteinases, and subsequently the membrane-tethered fragment is cleaved by presenilin/gamma-secretase, releasing its intracellular region into the cytoplasm; of note, the intracellular fragment of Ptprz shows nuclear localization.

Plasmin-mediated processing of protein tyrosine phosphatase receptor type Z in the mouse brain.

Protein tyrosine phosphatase receptor type Z (Ptprz, also known as PTPzeta or RPTPbeta) is preferentially expressed in the CNS as a major chondroitin sulfate proteoglycan (CSPG). Ptprz interacts with the PSD95 family through its intracellular carboxyl-terminal PDZ-binding motif in the postsynaptic density. Ptprz-deficient adult mice display impairments in spatial and contextual learning.

Tyrosine phosphorylation of ErbB4 is enhanced by PSD95 and repressed by protein tyrosine phosphatase receptor type Z.

Protein tyrosine phosphatase receptor type Z (Ptprz/PTPzeta/RPTPbeta) is a receptor-like protein tyrosine phosphatase (RPTP) preferentially expressed in the brain. ErbB4 is a member of the ErbB-family tyrosine kinases known as a neuregulin (NRG) receptor. Both are known to bind to postsynaptic density-95 (PSD95) on the second and the first/second PDZ (PSD95/Disc large/zona occludens1) domains, respectively, through the PDZ-binding motif of their carboxyl termini.