PTEN modulates EGFR late endocytic trafficking and degradation by dephosphorylating Rab7

Tumour suppressor phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a lipid phosphatase that negatively regulates growth factor-induced survival signalling. Here, we demonstrate that PTEN attenuates epidermal growth factor receptor (EGFR) signalling by promoting late endosome matur...

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Bibliographic Details
Published in:Nature communications 2016-02, Vol.7 (1), p.10689-10689, Article 10689
Main Authors: Shinde, Swapnil Rohidas, Maddika, Subbareddy
Format: Article
Language:English
Subjects:
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631/80/313/1461
631/80/458/1733
631/80/86
96/1
96/34
96/35
Blotting, Western
Cell Line, Tumor
Endocytosis
Endosomes - metabolism
Epidermal Growth Factor - metabolism
ErbB Receptors - metabolism
Fluorescent Antibody Technique
HEK293 Cells
HeLa Cells
Humanities and Social Sciences
Humans
Immunoprecipitation
multidisciplinary
Phosphoproteins - metabolism
Protein Transport
PTEN Phosphohydrolase - metabolism
rab GTP-Binding Proteins - metabolism
rab7 GTP-Binding Proteins
Science
Science (multidisciplinary)
Signal Transduction
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Summary:Tumour suppressor phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a lipid phosphatase that negatively regulates growth factor-induced survival signalling. Here, we demonstrate that PTEN attenuates epidermal growth factor receptor (EGFR) signalling by promoting late endosome maturation by virtue of its protein phosphatase activity. Loss of PTEN impairs the transition of ligand-bound EGFR from early to late endosomes. We unveil Rab7, a critical GTPase for endosome maturation, as a functional PTEN interacting partner. PTEN dephosphorylates Rab7 on two conserved residues S72 and Y183, which are necessary for GDP dissociation inhibitor (GDI)-dependent recruitment of Rab7 on to late endosomes and subsequent maturation. Thus, our findings reveal PTEN-dependent endosome maturation through phosphoregulation of Rab7 as an important route of controlling EGFR signalling. Rab7 is a critical GTPase for endosome maturation and it is implicated in the endocytic traffic of several receptors, including EGFR. In this study, the authors reveal the potential role of PTEN in the endocytic trafficking pathway of EGFR, which is dependent on its phosphatase activity through the direct post-translational modification of Rab7.
ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms10689