PAR3-APKC regulates Tiam1 by modulating suppressive internal interactions

Kenji Matsuzawa, Hiroki Akita, Takashi Watanabe, Mai Kakeno, Toshinori Matsui, Shujie Wang, Kozo Kaibuchi

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Tiam1 is one of the most extensively analyzed activators of the small GTPase Rac. However, fundamental aspects of its regulation are poorly understood. Here we demonstrate that Tiam1 is functionally suppressed by internal interactions and that the PAR complex participates in its full activation. The N-terminal region of Tiam1 binds to the protein-binding and catalytic domains to inhibit its localization and activation. Atypical PKCs phosphorylate Tiam1 to relieve its intramolecular interactions, and the subsequent stabilization of its interaction with PAR3 allows it to exert localized activity. By analyzing Tiam1 regulation by PAR3-APKC within the context of PDGF signaling, we also show that PAR3 directly binds PDGF receptor β. Thus we provide the first evidence for the negative regulation of Tiam1 by internal interactions, elucidate the nature of Tiam1 regulation by the PAR complex, and reveal a novel role for the PAR complex in PDGF signaling.

Original languageEnglish
Pages (from-to)1511-1523
Number of pages13
JournalMolecular Biology of the Cell
Volume27
Issue number9
DOIs
Publication statusPublished - 01-05-2016
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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