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Pharmacological inhibition of pleckstrin homology domain leucine-rich repeat protein phosphatase is neuroprotective: differential effects on astrocytes.

Jackson TC, Verrier JD, Drabek T, Janesko-Feldman K, Gillespie DG, Uray T, Dezfulian C, Clark RS, Bayir H, Jackson EK, Kochanek PM.

J Pharmacol Exp Ther. 2013 Nov;347(2):516-28. doi: 10.1124/jpet.113.206888. Epub 2013 Sep 10.


PHLPP1 gene deletion protects the brain from ischemic injury.

Chen B, Van Winkle JA, Lyden PD, Brown JH, Purcell NH.

J Cereb Blood Flow Metab. 2013 Feb;33(2):196-204. doi: 10.1038/jcbfm.2012.150. Epub 2012 Oct 17.


Discovery of small molecule inhibitors of the PH domain leucine-rich repeat protein phosphatase (PHLPP) by chemical and virtual screening.

Sierecki E, Sinko W, McCammon JA, Newton AC.

J Med Chem. 2010 Oct 14;53(19):6899-911. doi: 10.1021/jm100331d.


Assembly of the FKBP51-PHLPP2-AKT signaling complex in cerebral ischemia/reperfusion injury in rats.

Wei XE, Zhang FY, Wang K, Zhang QX, Rong LQ.

Brain Res. 2014 May 30;1566:60-8. doi: 10.1016/j.brainres.2014.04.009. Epub 2014 Apr 16.


PHLPP is a negative regulator of RAF1, which reduces colorectal cancer cell motility and prevents tumor progression in mice.

Li X, Stevens PD, Liu J, Yang H, Wang W, Wang C, Zeng Z, Schmidt MD, Yang M, Lee EY, Gao T.

Gastroenterology. 2014 May;146(5):1301-12.e1-10. doi: 10.1053/j.gastro.2014.02.003. Epub 2014 Feb 11.


Depletion of Pleckstrin homology domain leucine-rich repeat protein phosphatases 1 and 2 by Bcr-Abl promotes chronic myelogenous leukemia cell proliferation through continuous phosphorylation of Akt isoforms.

Hirano I, Nakamura S, Yokota D, Ono T, Shigeno K, Fujisawa S, Shinjo K, Ohnishi K.

J Biol Chem. 2009 Aug 14;284(33):22155-65. doi: 10.1074/jbc.M808182200. Epub 2009 Mar 4.


Purinergic receptor-mediated rapid depletion of nuclear phosphorylated Akt depends on pleckstrin homology domain leucine-rich repeat phosphatase, calcineurin, protein phosphatase 2A, and PTEN phosphatases.

Mistafa O, Ghalali A, Kadekar S, Högberg J, Stenius U.

J Biol Chem. 2010 Sep 3;285(36):27900-10. doi: 10.1074/jbc.M110.117093. Epub 2010 Jul 6.


PTEN, NHERF1 and PHLPP form a tumor suppressor network that is disabled in glioblastoma.

Molina JR, Agarwal NK, Morales FC, Hayashi Y, Aldape KD, Cote G, Georgescu MM.

Oncogene. 2012 Mar 8;31(10):1264-74. doi: 10.1038/onc.2011.324. Epub 2011 Aug 1.


The phosphatase PHLPP controls the cellular levels of protein kinase C.

Gao T, Brognard J, Newton AC.

J Biol Chem. 2008 Mar 7;283(10):6300-11. Epub 2007 Dec 27.


PHLPP1 splice variants differentially regulate AKT and PKCα signaling in hippocampal neurons: characterization of PHLPP proteins in the adult hippocampus.

Jackson TC, Verrier JD, Semple-Rowland S, Kumar A, Foster TC.

J Neurochem. 2010 Nov;115(4):941-55. doi: 10.1111/j.1471-4159.2010.06984.x. Epub 2010 Sep 28.


Diacylglycerol kinase δ modulates Akt phosphorylation through pleckstrin homology domain leucine-rich repeat protein phosphatase 2 (PHLPP2).

Crotty TM, Nakano T, Stafforini DM, Topham MK.

J Biol Chem. 2013 Jan 18;288(3):1439-47. doi: 10.1074/jbc.M112.407379. Epub 2012 Nov 26.


PHLiPPing the switch on Akt and protein kinase C signaling.

Brognard J, Newton AC.

Trends Endocrinol Metab. 2008 Aug;19(6):223-30. doi: 10.1016/j.tem.2008.04.001. Epub 2008 May 27. Review.


PHLPPing through history: a decade in the life of PHLPP phosphatases.

Grzechnik AT, Newton AC.

Biochem Soc Trans. 2016 Dec 15;44(6):1675-1682. Review.


Cell type-specific dependency on the PI3K/Akt signaling pathway for the endogenous Epo and VEGF induction by baicalein in neurons versus astrocytes.

Sun YY, Lin SH, Lin HC, Hung CC, Wang CY, Lin YC, Hung KS, Lien CC, Kuan CY, Lee YH.

PLoS One. 2013 Jul 19;8(7):e69019. doi: 10.1371/journal.pone.0069019. Print 2013.


Paeoniflorin ameliorates ischemic neuronal damage in vitro via adenosine A1 receptor-mediated transactivation of epidermal growth factor receptor.

Zhong M, Song WL, Xu YC, Ye Y, Feng LY.

Acta Pharmacol Sin. 2015 Mar;36(3):298-310. doi: 10.1038/aps.2014.154. Epub 2015 Feb 9.


The phosphatase PHLPP1 regulates Akt2, promotes pancreatic cancer cell death, and inhibits tumor formation.

Nitsche C, Edderkaoui M, Moore RM, Eibl G, Kasahara N, Treger J, Grippo PJ, Mayerle J, Lerch MM, Gukovskaya AS.

Gastroenterology. 2012 Feb;142(2):377-87.e1-5. doi: 10.1053/j.gastro.2011.10.026. Epub 2011 Oct 29.


Loss of PHLPP expression in colon cancer: role in proliferation and tumorigenesis.

Liu J, Weiss HL, Rychahou P, Jackson LN, Evers BM, Gao T.

Oncogene. 2009 Feb 19;28(7):994-1004. doi: 10.1038/onc.2008.450. Epub 2008 Dec 15.


Direct protection of neurons and astrocytes by matrine via inhibition of the NF-κB signaling pathway contributes to neuroprotection against focal cerebral ischemia.

Xu M, Yang L, Hong LZ, Zhao XY, Zhang HL.

Brain Res. 2012 May 15;1454:48-64. doi: 10.1016/j.brainres.2012.03.020. Epub 2012 Mar 15.


Turning off AKT: PHLPP as a drug target.

Newton AC, Trotman LC.

Annu Rev Pharmacol Toxicol. 2014;54:537-58. doi: 10.1146/annurev-pharmtox-011112-140338. Review.

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