Protein tyrosine phosphatase receptor type Z is inactivated by ligand-induced oligomerization.
Receptor-type protein tyrosine phosphatases (RPTPs) are considered to transduce extracellular signals across the membrane through changes in their PTP activity, however, our understanding of the regulatory mechanism is still limited. Here, we show that pleiotrophin (PTN), a natural ligand for protein tyrosine phosphatase receptor type Z (Ptprz) (also called PTPzeta/RPTPbeta), inactivates Ptprz through oligomerization and increases the tyrosine phosphorylation of substrates for Ptprz, G protein-coupled receptor kinase-interactor 1 (Git1) and membrane associated guanylate kinase, WW and PDZ domain containing 1 (Magi1). Oligomerization of Ptprz by an artificial dimerizer or polyclonal antibodies against its extracellular region also leads to inactivation, indicating that Ptprz is active in the monomeric form and inactivated by ligand-induced oligomerization.
Fukada
Masahide
M
Division of Molecular Neurobiology, National Institute for Basic Biology, 5-1 Higashiyama, Myodaiji-cho, Okazaki, Aichi 444-8787, Japan.
Fujikawa
Akihiro
A
Chow
Jeremy P H
JP
Ikematsu
Shinya
S
Sakuma
Sadatoshi
S
Noda
Masaharu
M
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism* / Q000494:pharmacology; D002460:Cell Line; D006224:Cricetinae; D016207:Cytokines / Q000378:metabolism* / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D008024:Ligands; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D011940:Receptor Aggregation / Q000187:drug effects / Q000502:physiology*; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5
D048868:Adaptor Proteins, Signal Transducing; D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D016207:Cytokines; D008024:Ligands; C066845:pleiotrophin; D017027:Protein Tyrosine Phosphatases; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5