Fyn is a downstream target of the pleiotrophin/receptor protein tyrosine phosphatase 脙脙脙脙/脙脙脙脙-signaling pathway: Regulation of tyrosine phosphorylation of Fyn by pleiotrophin
摘要
Pleiotrophin (PTN the protein, Ptn the gene) signals downstream targets through inactivation of its receptor, the transmembrane receptor protein tyrosine phosphatase (RPTP)β/ζ, disrupting the balanced activity of RPTPβ/ζ and the activity of a constitutively active tyrosine kinase. As a consequence of the inactivation of RPTPβ/ζ, PTN stimulates a sharp increase in the levels of tyrosine phosphorylation of the substrates of RPTPβ/ζ in PTN-stimulated cells. We now report that the Src family member Fyn interacts with the intracellular domain of RPTPβ/ζ in a yeast two-hybrid system. We further demonstrate that Fyn is a substrate of RPTPβ/ζ, and that tyrosine phosphorylation of Fyn is sharply increased in PTN-stimulated cells. In previous studies, we demonstrated that β-catenin and β-adducin are targets of the PTN/RPTPβ/ζ-signaling pathway and defined the mechanisms through which tyrosine phosphorylation of β-catenin and β-adducin disrupts cytoskeletal protein complexes. We conclude that Fyn is a downstream target of the PTN/RPTPβ/ζ-signaling pathway and suggest that PTN coordinately regulates tyrosine phosphorylation of β-catenin, β-adducin, and Fyn through the PTN/RPTPβ/ζ-signaling pathway and that together Fyn, β-adducin, and β-catenin may be effectors of the previously described PTN-stimulated disruption of cytoskeletal stability, increased cell plasticity, and loss of cell–cell adhesion that are characteristic of PTN-stimulated cells and a feature of many human malignant cells in which mutations have established constitutive expression of the Ptn gene.