Characterization of PXK as a protein involved in epidermal growth factor receptor trafficking

Hiroshi Takeuchi, Takako Takeuchi, Jing Gao, Lewis C. Cantley, Masato Hirata

研究成果: Contribution to journalArticle査読

21 被引用数 (Scopus)

抄録

The phox homology (PX) domain is a phosphoinositide-binding module that typically binds phosphatidylinositol 3-phosphate. Out of 47 mammalian proteins containing PX domains, more than 30 are denoted sorting nexins and several of these have been implicated in internalization of cell surface proteins to the endosome, where phosphatidylinositol-3-phosphate is concentrated. Here we investigated a multimodular protein termed PXK, composed of a PX domain, a protein kinase-like domain, and a WASP homology 2 domain. We show that the PX domain of PXK localizes this protein to the endosomal membrane via binding to phosphatidylinositol 3-phosphate. PXK expression in COS7 cells accelerated the ligand-induced internalization and degradation of epidermal growth factor receptors by a mechanism requiring phosphatidylinositol 3-phosphate binding but not involving the WASP homology 2 domain. Conversely, depletion of PXK using RNA interference decreased the rate of epidermal growth factor receptor internalization and degradation. Ubiquitination of epidermal growth factor receptor by the ligand stimulation was enhanced in PXK-expressing cells. These results indicate that PXK plays a critical role in epidermal growth factor receptor trafficking through modulating ligand-induced ubiquitination of the receptor.

本文言語英語
ページ(範囲)1689-1702
ページ数14
ジャーナルMolecular and cellular biology
30
7
DOI
出版ステータス出版済み - 4 2010

All Science Journal Classification (ASJC) codes

  • 分子生物学
  • 細胞生物学

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