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

First Author  Li X Year  2011
Journal  EMBO Rep Volume  12
Issue  8 Pages  818-24
PubMed ID  21701506 Mgi Jnum  J:200493
Mgi Id  MGI:5508722 Doi  10.1038/embor.2011.106
Citation  Li X, et al. (2011) Scribble-mediated membrane targeting of PHLPP1 is required for its negative regulation of Akt. EMBO Rep 12(8):818-24
abstractText  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.
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