title: Scribble-mediated membrane targeting of PHLPP1 is required for its negative regulation of Akt.
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.
authors.affiliation: Markey Cancer Center, University of Kentucky, Lexington, Kentucky 40536, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Haihua
authors.initials: H
authors.lastname: Yang
authors.forename: Jianyu
authors.initials: J
authors.lastname: Liu
authors.forename: Micheal D
authors.initials: MD
authors.lastname: Schmidt
authors.forename: Tianyan
authors.initials: T
authors.lastname: Gao
mesh_terms: D018938:Caco-2 Cells; D048708:Cell Growth Processes / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D055785:Gene Knockdown Techniques / Q000379:methods; D045325:HCT116 Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D054731:PDZ Domains; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D009687:Nuclear Proteins; C480591:SCRIB protein, human; D025521:Tumor Suppressor Proteins; D051057:Proto-Oncogene Proteins c-akt; C400601:PHLPP1 protein, human; D010749:Phosphoprotein Phosphatases