Fyn is a downstream target of the pleiotrophin/receptor protein tyrosine phosphatase beta/zeta-signaling pathway: regulation of tyrosine phosphorylation of Fyn by pleiotrophin.
Pleiotrophin (PTN the protein, Ptn the gene) signals downstream targets through inactivation of its receptor, the transmembrane receptor protein tyrosine phosphatase (RPTP)beta/zeta, disrupting the balanced activity of RPTPbeta/zeta and the activity of a constitutively active tyrosine kinase. As a consequence of the inactivation of RPTPbeta/zeta, PTN stimulates a sharp increase ... in the levels of tyrosine phosphorylation of the substrates of RPTPbeta/zeta in PTN-stimulated cells. We now report that the Src family member Fyn interacts with the intracellular domain of RPTPbeta/zeta in a yeast two-hybrid system. We further demonstrate that Fyn is a substrate of RPTPbeta/zeta, and that tyrosine phosphorylation of Fyn is sharply increased in PTN-stimulated cells. In previous studies, we demonstrated that beta-catenin and beta-adducin are targets of the PTN/RPTPbeta/zeta-signaling pathway and defined the mechanisms through which tyrosine phosphorylation of beta-catenin and beta-adducin disrupts cytoskeletal protein complexes. We conclude that Fyn is a downstream target of the PTN/RPTPbeta/zeta-signaling pathway and suggest that PTN coordinately regulates tyrosine phosphorylation of beta-catenin, beta-adducin, and Fyn through the PTN/RPTPbeta/zeta-signaling pathway and that together Fyn, beta-adducin, and beta-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.
Mesh Terms:
Binding Sites, Carrier Proteins, Cytokines, Humans, In Vitro Techniques, Nerve Tissue Proteins, Phosphorylation, Protein Structure, Tertiary, Protein Tyrosine Phosphatases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-fyn, Receptor-Like Protein Tyrosine Phosphatases, Class 5, Recombinant Proteins, Signal Transduction, Substrate Specificity, Two-Hybrid System Techniques, Tyrosine, src-Family Kinases
Binding Sites, Carrier Proteins, Cytokines, Humans, In Vitro Techniques, Nerve Tissue Proteins, Phosphorylation, Protein Structure, Tertiary, Protein Tyrosine Phosphatases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-fyn, Receptor-Like Protein Tyrosine Phosphatases, Class 5, Recombinant Proteins, Signal Transduction, Substrate Specificity, Two-Hybrid System Techniques, Tyrosine, src-Family Kinases
Biochem. Biophys. Res. Commun.
Date: Jul. 08, 2005
PubMed ID: 15925565
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