Pleiotrophin regulates serine phosphorylation and the cellular distribution of β-adducin through activation of protein kinase C

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

Research output: Contribution to journalArticlepeer-review

Abstract

Pleiotrophin (PTN) was found to regulate tyrosine phosphorylation of β-adducin through the PTN/receptor protein tyrosine phosphatase (RPTP)β/ζ signaling pathway. We now demonstrate that PTN stimulates the phosphorylation of serines 713 and 726 in the myristoylated alanine-rich protein kinase (PK) C substrate domain of β-adducin through activation of either PKC α or β. We also demonstrate that PTN stimulates translocation of phosphoserine 713 and 726 β-adducin either to nuclei, where it associates with nuclear chromatin and with centrioles of dividing cells, or to a membrane-associated site, depending on the phase of cell growth. Furthermore, we demonstrate that PTN stimulates the degradation of β-adducin in PTN-stimulated cells. Phosphorylation of serines 713 and 726 in β-adducin is known to markedly reduce the affinity of β-adducin for spectrin and actin and to uncouple actin/spectrin/ β-adducin multimeric complexes needed for cytoskeletal stability. The data thus suggest that the PTN-stimulated phosphorylation of serines 713 and 726 in β-adducin disrupts cytoskeletal protein complexes and integrity, features demonstrated in both PTN-stimulated cells and of highly malignant cells that constitutively express the endogenous Ptn gene. The data also support the important conclusion that PTN determines the cellular location of β-adducin phosphorylated in serines 713 and 726 and raise the possibility that β-adducin functions in support of structure of heterochromatin and centrioles during mitosis.

Original languageEnglish (US)
Pages (from-to)12407-12412
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number35
DOIs
StatePublished - Aug 30 2005
Externally publishedYes

ASJC Scopus subject areas

  • General

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