基于实验室在2005年的研究成果，加州大学医学院的研究者如今识别出了可作为治疗糖尿病、心脏病和神经系统疾病的靶点酶（enzyme）的另外两个突变体。此项研究是由药理学教授Alexandra C. Newton和他的同事一起完成的，文章发表在最新一期的《分子细胞》（Molecular Cell）杂志上。
之前，同样由Newton所做的研究成果也发表在《分子细胞》杂志上。在那篇文章中，作者发现了一种酶——PHLPP（PH domain Leucine-rich repeat Protein Phosphatase)，该酶可以关闭 Akt/蛋白激酶B（该蛋白调控着细胞生长、增殖和生存）的信号。
新的研究工作描述了该家族的第二位成员：PHLPP2。PHLPP2同样可以让Akt失活，从而抑制细胞周期，促使细胞死亡。但是，PHLPP1和PHLPP2调控着三种不同的疾病通路：PHLPP1在糖尿病治疗中起着重要的作用，PHLPP2在治疗心脏病和神经系统疾病上可能有着重要应用价值。
部分英文原文：
Molecular Cell, Vol 25, 917-931, 23 March 2007
Article
PHLPP and a Second Isoform, PHLPP2, Differentially Attenuate the Amplitude of Akt Signaling by Regulating Distinct Akt Isoforms
John Brognard,1,2 Emma Sierecki,1 Tianyan Gao,1,3 and Alexandra C. Newton1,
1 Department of Pharmacology, University of California at San Diego, La Jolla, CA 92093, USA
2 Biomedical Sciences Graduate Program, University of California at San Diego, La Jolla, CA 92093, USA
Corresponding author
Alexandra C. Newton
anewton@ucsd.edu
Akt/protein kinase B controls cell growth, proliferation, and survival. We recently discovered a novel phosphatase PHLPP, for PH domain leucine-rich repeat protein phosphatase, which terminates Akt signaling by directly dephosphorylating and inactivating Akt. Here we describe a second family member, PHLPP2, which also inactivates Akt, inhibits cell-cycle progression, and promotes apoptosis. These phosphatases control the amplitude of Akt signaling: depletion of either isoform increases the magnitude of agonist-evoked Akt phosphorylation by almost two orders of magnitude. Although PHLPP1 and PHLPP2 both dephosphorylate the same residue (hydrophobic phosphorylation motif) on Akt, they differentially terminate Akt signaling by regulating distinct Akt isoforms. Knockdown studies reveal that PHLPP1 specifically modulates the phosphorylation of HDM2 and GSK-3α through Akt2, whereas PHLPP2 specifically modulates the phosphorylation of p27 through Akt3. Our data unveil a mechanism to selectively terminate Akt-signaling pathways through the differential inactivation of specific Akt isoforms by specific PHLPP isoforms.
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