Pleiotrophin stimulates tyrosine phosphorylation of β-adducin through inactivation of the transmembrane receptor protein tyrosine phosphatase β/ζ

Harold Pariser, Pablo Perez-Pinera, Laura Ezquerra, Gonzalo Herradon, Thomas F. Deuel

Research output: Contribution to journalArticlepeer-review

Abstract

Pleiotrophin (PTN the protein, Ptn the gene) signals through a unique mechanism; it inactivates the tyrosine phosphatase activity of its receptor, the transmembrane receptor protein tyrosine phosphatase (RPTP)β/ζ, and increases tyrosine phosphorylation of the substrates of RPTPβ/ζ through the continued activity of a yet to be described protein tyrosine kinase(s) in PTN-stimulated cells. We have now found that the cytoskeletal protein β-adducin interacts with the intracellular domain of RPTPβ/ζ in a yeast two-hybrid system, that β-adducin is a substrate of RPTPβ/ζ, that β-adducin is phosphorylated in tyrosine in cells not stimulated by PTN, and that tyrosine phosphorylation of β-adducin is sharply increased in PTN-stimulated cells, suggesting that β-adducin is a downstream target of and regulated by the PTN/RPTPβ/ζ signaling pathway. β-Catenin was the first downstream target of the PTN/RPTPβ/ζ signaling pathway to be identified; these data thus also suggest that PTN coordinately regulates steady state levels of tyrosine phosphorylation of the important cytoskeletal proteins β-adducin and β-catenin and, through PTN-stimulated tyrosine phosphorylation, β-adducin may contribute to the disruption of cytoskeletal structure, increased plasticity, and loss of homophilic cell-cell adhesion that are the consequences of PTN stimulation of cells and a characteristic feature of different malignant cells with mutations that activate constitutive expression of the endogenous Ptn gene.

Original languageEnglish (US)
Pages (from-to)232-239
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume335
Issue number1
DOIs
StatePublished - Sep 16 2005
Externally publishedYes

Keywords

  • β-Adducin
  • Pleiotrophin
  • Receptor protein tyrosine phosphatase β/ζ

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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