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EMBO Rep. 2011 Jun 24;12(8):818-24. doi: 10.1038/embor.2011.106.

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

Author information

1
Markey Cancer Center, University of Kentucky, Lexington, Kentucky 40536, USA.

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.

PMID:
21701506
PMCID:
PMC3147256
DOI:
10.1038/embor.2011.106
[Indexed for MEDLINE]
Free PMC Article

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