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PTEN modulates EGFR late endocytic trafficking and degradation by dephosphorylating Rab7

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  • Swapnil Rohidas Shinde

    (Laboratory of Cell Death and Cell Survival, Centre for DNA Fingerprinting and Diagnostics (CDFD)
    Graduate Studies, Manipal University)

  • Subbareddy Maddika

    (Laboratory of Cell Death and Cell Survival, Centre for DNA Fingerprinting and Diagnostics (CDFD))

Abstract

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.

Suggested Citation

  • Swapnil Rohidas Shinde & Subbareddy Maddika, 2016. "PTEN modulates EGFR late endocytic trafficking and degradation by dephosphorylating Rab7," Nature Communications, Nature, vol. 7(1), pages 1-11, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10689
    DOI: 10.1038/ncomms10689
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    Cited by:

    1. Carla Abrahamian & Rachel Tang & Rebecca Deutsch & Lina Ouologuem & Eva-Maria Weiden & Veronika Kudrina & Julia Blenninger & Julia Rilling & Colin Feldmann & Solveig Kuss & Youli Stepanov & Anna Scott, 2024. "Rab7a is an enhancer of TPC2 activity regulating melanoma progression through modulation of the GSK3β/β-Catenin/MITF-axis," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Shin-Jin Lin & Ming-Chieh Lin & Tsai-Jung Liu & Yueh-Tso Tsai & Ming-Ting Tsai & Fang-Jen S. Lee, 2023. "Endosomal Arl4A attenuates EGFR degradation by binding to the ESCRT-II component VPS36," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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