PHLPP: a phosphatase that directly dephosphorylates Akt, promotes apoptosis, and suppresses tumor growth.

By Tianyan Gao, F. Furnari, A. Newton. Molecules and Cells, 2005

940 citations recorded by the source corpus.

Subfields: Molecular Biology, Pathology and Forensic Medicine

View Paper: https://www.semanticscholar.org/paper/2587476cad6a3e15ddedadc2d6fd030a03cbd723

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

1. David M. Sabatini
2. T. Franke
3. P. Pandolfi
4. Lewis C. Cantley
5. R. Shaw
6. Arkaitz Carracedo
7. Ping Wee
8. Zhixiang Wang

In Pathology and Forensic Medicine

1. David M. Sabatini
2. A. Newton
3. Ping Wee
4. Zhixiang Wang
5. C. Sawyers
6. R. Shaw
7. P. Pandolfi

Citations in the corpus

• The PI3K/AKT pathway in obesity and type 2 diabetes (2018, background): “Protein phosphatase 2A (PP2A) [23] and PH domain leucine-rich repeat protein phosphatases (PHLPP1 and PHLPP2) [24] dephosphorylate AKT T308 and S473, respectively, leading to AKT inactivation.”
• The Molecular Bases of Training Adaptation (2007, background): “Of late, a PH domain leucine-rich repeat protein phosphatase (PHLPP) has been shown to dephosphorylate AKT and suppress growth in cancer cells but this down-regulation of AKT has yet to be confirmed in skeletal muscle (Gao et al. 2005).”
• Serine/threonine phosphatases: mechanism through structure. (2009, background): “PHLPP and PHLPP2 are thought to promote apoptosis and suppress tumor growth through dephosphorylation of distinct Akt isoforms (Brognard et al., 2007; Gao et al., 2005).”
• Defining the role of mTOR in cancer. (2007, background): “The recently described PHLPP phosphatases (PHLPP1 and PHLPP2) counteract mTORC2 by dephosphorylating AKT at S473 (Brognard et al., 2007; Gao et al., 2005).”
• PI3K/Akt: getting it right matters (2008, background): “, 2007), Src (Jiang and Qiu, 2003) and both known isoforms of the PH domain leucine-rich repeat protein phosphatase family (PHLPP) (Gao et al., 2005; Brognard et al., 2007).”
• PHLPP and a second isoform, PHLPP2, differentially attenuate the amplitude of Akt signaling by regulating distinct Akt isoforms. (2007, methodology): “To determine G1/S ratios, cells were cotransfected with GFP and HA-PHLPP2 and incubated with high serum (10% FBS) for 48 hr; cells were gated based on GFP expression as described previously (Gao et al., 2005).”
• Integrative genomic profiling of human prostate cancer (2010, background): “implicated in PI3K regulation, the PIK3CA gene itself, and the PIK3CA regulatory subunits PIK3R1 and PIK3R3 (Cancer Genome Atlas Research Network, 2008; Gao et al., 2005; Gewinner et al., 2009; Jaiswal et al., 2009; Ueki et al., 2003).”
• The PTEN–PI3K pathway: of feedbacks and cross-talks (2008, background): “On the one hand, protein phosphatase (PP) 2A dephosphorylates primarily Thr308, whereas the phosphatase PHLPP dephosphorylates Ser473 (Bayascas and Alessi, 2005; Gao et al., 2005).”
• Tenets of PTEN tumor suppression. (2008, background): “pho-Ser473 on AKT (Brognard et al., 2007; Gao et al., 2005).”
• Epidermal Growth Factor Receptor Cell Proliferation Signaling Pathways (2017, background): “Once localized at the PM, AKT is phosphorylated at T308 and S473.”
• Reciprocal feedback regulation of PI3K and androgen receptor signaling in PTEN-deficient prostate cancer. (2011, background): “The immunophilin FKBP5 is a chaperone for the AKT phosphatase PHLPP, and its expression in prostate cancer is androgen dependent (Gao et al., 2005; Pei et al., 2009).”
• In B cells, phosphatidylinositol 5-phosphate 4-kinase–α synthesizes PI(4,5)P2 to impact mTORC2 and Akt signaling (2016, background): “for removing the Ser473 phosphate of Akt and the Ser422 phosphate of SGK1 (17, 18) support PI5P4Kα being a negative regulator of mTORC2 as more likely than a positive regulator of two different phosphatases.”
• Ras, PI(3)K and mTOR signalling controls tumour cell growth (2006, background): “PHLPP, a newly identified phosphatase containing a lipid-binding PH (pleckstrin homology) domain, specifically dephosphorylates Ser 473 of AK”
• Critical nodes in signalling pathways: insights into insulin action (2006, background): “AKT/PKB activity is regulated by several inhibitory molecules, including enzymes like the protein phosphatase-2A (PP2A) and the PH-domain leucine-rich repeat protein phosphatase (PHLPP), which directly dephosphorylate and deactivate AKT/PK”