Pleiotrophin Stimulates Tyrosine Phosphorylation of Beta-Adducin Through Inactivation of the Transmembrane Receptor Protein Tyrosine Phosphatase beta/zeta

Biochem Biophys Res Commun. 2005 Sep 16;335(1):232-9. doi: 10.1016/j.bbrc.2005.07.060.


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)beta/zeta, and increases tyrosine phosphorylation of the substrates of RPTPbeta/zeta 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 beta-adducin interacts with the intracellular domain of RPTPbeta/zeta in a yeast two-hybrid system, that beta-adducin is a substrate of RPTPbeta/zeta, that beta-adducin is phosphorylated in tyrosine in cells not stimulated by PTN, and that tyrosine phosphorylation of beta-adducin is sharply increased in PTN-stimulated cells, suggesting that beta-adducin is a downstream target of and regulated by the PTN/RPTPbeta/zeta signaling pathway. beta-Catenin was the first downstream target of the PTN/RPTPbeta/zeta 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 beta-adducin and beta-catenin and, through PTN-stimulated tyrosine phosphorylation, beta-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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Calmodulin-Binding Proteins / chemistry
  • Calmodulin-Binding Proteins / genetics
  • Calmodulin-Binding Proteins / metabolism*
  • Carrier Proteins / pharmacology*
  • Cell Line
  • Cytokines / pharmacology*
  • Enzyme Activation / drug effects
  • Humans
  • Molecular Sequence Data
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Peptide Fragments / chemistry
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism
  • Phosphorylation / drug effects
  • Phosphotyrosine / metabolism*
  • Protein Binding
  • Protein Tyrosine Phosphatases / genetics
  • Protein Tyrosine Phosphatases / metabolism*
  • Receptor-Like Protein Tyrosine Phosphatases, Class 5
  • Saccharomyces cerevisiae / chemistry
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Sequence Alignment
  • Substrate Specificity
  • Two-Hybrid System Techniques


  • Calmodulin-Binding Proteins
  • Carrier Proteins
  • Cytokines
  • Nerve Tissue Proteins
  • Peptide Fragments
  • adducin
  • pleiotrophin
  • Phosphotyrosine
  • PTPRZ1 protein, human
  • Protein Tyrosine Phosphatases
  • Receptor-Like Protein Tyrosine Phosphatases, Class 5