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Protein tyrosine phosphatase receptor type Z is inactivated by ligand-induced oligomerization

Masahide Fukada1, Akihiro Fujikawa, Jeremy P H Chow

  • 1Division of Molecular Neurobiology, National Institute for Basic Biology, 5-1 Higashiyama, Myodaiji-cho, Okazaki, Aichi 444-8787, Japan.

FEBS Letters
|July 4, 2006
PubMed

Insights

Pleiotrophin (PTN) inactivates the protein tyrosine phosphatase receptor type Z (Ptprz) by inducing its oligomerization. This mechanism reveals Ptprz is active as a monomer and regulated by ligand-induced dimerization.

Area of Science:

  • Cellular signaling
  • Molecular biology
  • Biochemistry

Background:

  • Receptor-type protein tyrosine phosphatases (RPTPs) mediate extracellular signals via PTP activity.
  • Regulatory mechanisms of RPTPs, including Ptprz, remain incompletely understood.

Purpose of the Study:

  • To elucidate the regulatory mechanism of protein tyrosine phosphatase receptor type Z (Ptprz).
  • To investigate the role of pleiotrophin (PTN) in Ptprz regulation.

Main Methods:

  • Investigated the interaction between PTN and Ptprz.
  • Utilized artificial dimerizers and antibodies to induce Ptprz oligomerization.
  • Assessed tyrosine phosphorylation levels of Ptprz substrates (Git1, Magi1).

Main Results:

  • Pleiotrophin (PTN) binding inactivates Ptprz through induced oligomerization.
  • Oligomerization of Ptprz, whether by PTN, artificial dimerizers, or antibodies, leads to its inactivation.
  • Ptprz inactivation increases tyrosine phosphorylation of its substrates, Git1 and Magi1.

Conclusions:

  • Ptprz is active in its monomeric form.
  • Ligand-induced oligomerization is a key mechanism for Ptprz inactivation.
  • This finding provides insight into RPTP regulation and signal transduction pathways.

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