Dimerization of tyrosine phosphatase PTPRO decreases its activity and ability to inactivate TrkC

Amy E. Hower, Pedro J. Beltran, John L. Bixby

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Receptor-protein tyrosine phosphatases (RPTPs), like receptor tyrosine kinases, regulate neuronal differentiation. While receptor tyrosine kinases are dimerized and activated by extracellular ligands, the extent to which RPTPs dimerize, and the effects of dimerization on phosphatase activity, are poorly understood. We have examined a neuronal type III RPTP, PTPRO; we find that PTPRO can form dimers in living cells, and that disulfide linkages in PTPROs intracellular domain likely regulate dimerization. Dimerization of PTPROs transmembrane and intracellular domains, achieved by ligand binding to a chimeric fusion protein, decreases activity toward artificial peptides and toward a putative substrate, tropomyosin-related kinase C (TrkC). Dephosphorylation of TrkC by PTPRO may be physiologically relevant, as it is efficient, and TrkC and PTPRO can be co-precipitated from transfected cells. Inhibition of PTPROs phosphatase activity by dimerization is interesting, as dimerization of a related RPTP, CD148/PTPRJ, increases activity. Thus, our results suggest a complex relationship between dimerization and activity in type III RPTPs.

Original languageEnglish (US)
Pages (from-to)1635-1647
Number of pages13
JournalJournal of neurochemistry
Volume110
Issue number5
DOIs
StatePublished - Sep 2009

Keywords

  • CD148
  • Cell adhesion
  • CRYP-2
  • Neurotrophin
  • Protein tyrosine phosphatase
  • Tyrosine phosphorylation

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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