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

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

Research output: Contribution to journalArticle

20 Citations (Scopus)

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
Pages (from-to)1635-1647
Number of pages13
JournalJournal of Neurochemistry
Volume110
Issue number5
DOIs
StatePublished - Sep 1 2009

Fingerprint

Class 3 Receptor-Like Protein Tyrosine Phosphatases
Tropomyosin
Dimerization
Tyrosine
Protein Tyrosine Phosphatases
Phosphotransferases
Receptor Protein-Tyrosine Kinases
Receptor-Like Protein Tyrosine Phosphatases
Ligands
Phosphoric Monoester Hydrolases
Disulfides
Dimers
tropomyosin kinase
Fusion reactions
Cells
Peptides

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Dimerization of tyrosine phosphatase PTPRO decreases its activity and ability to inactivate TrkC. / Hower, Amy E.; Beltran, Pedro J.; Bixby, John.

In: Journal of Neurochemistry, Vol. 110, No. 5, 01.09.2009, p. 1635-1647.

Research output: Contribution to journalArticle

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