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

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

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1689-1702
Number of pages14
JournalMolecular and cellular biology
Volume30
Issue number7
DOIs
Publication statusPublished - Apr 1 2010

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Epidermal Growth Factor Receptor
Ubiquitination
Ligands
Sorting Nexins
Proteins
Endosomes
Phosphatidylinositols
RNA Interference
Protein Kinases
Membrane Proteins
Membranes
phosphatidylinositol 3-phosphate
4-ethoxymethylene-2-phenyl-2-oxazoline-5-one

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Characterization of PXK as a protein involved in epidermal growth factor receptor trafficking. / Takeuchi, Hiroshi; Takeuchi, Takako; Gao, Jing; Cantley, Lewis C.; Hirata, Masato.

In: Molecular and cellular biology, Vol. 30, No. 7, 01.04.2010, p. 1689-1702.

Research output: Contribution to journalArticle

Takeuchi, Hiroshi ; Takeuchi, Takako ; Gao, Jing ; Cantley, Lewis C. ; Hirata, Masato. / Characterization of PXK as a protein involved in epidermal growth factor receptor trafficking. In: Molecular and cellular biology. 2010 ; Vol. 30, No. 7. pp. 1689-1702.
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