Scribble-mediated membrane targeting of PHLPP1 is required for its negative regulation of Akt

Xin Li, Haihua Yang, Jianyu Liu, Micheal D. Schmidt, Tianyan Gao

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

Abstract

PHLPP1 (PH domain leucine-rich-repeats protein phosphatase) is a Ser/Thr protein phosphatase that acts as a tumour suppressor by negatively regulating Akt. Here, we show that PHLPP1 is recruited to the cell membrane by binding to a scaffolding protein: Scribble. Knockdown of Scribble (Scrib) results in redistribution of PHLPP1 from the membrane to the cytoplasm and an increase in Akt phosphorylation, whereas overexpression of Scrib has the opposite effect. Furthermore, PHLPP1-dependent inhibition of cell proliferation is facilitated by the formation of a Scrib, PHLPP1 and Akt trimeric complex. Thus, our findings identify a functional interaction between PHLPP1 and Scrib in negatively regulating Akt signalling.

Original languageEnglish
Pages (from-to)818-824
Number of pages7
JournalEMBO Reports
Volume12
Issue number8
DOIs
StatePublished - Aug 2011

Keywords

  • Akt phosphorylation
  • PHLPP
  • Scribble
  • scaffolding protein

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics

Fingerprint

Dive into the research topics of 'Scribble-mediated membrane targeting of PHLPP1 is required for its negative regulation of Akt'. Together they form a unique fingerprint.

Cite this