PH domain leucine-rich repeat-containing protein phosphatase 2

Definition:

Protein phosphatase involved in regulation of Akt and PKC signaling. Mediates dephosphorylation in the C-terminal domain hydrophobic motif of members of the AGC Ser/Thr protein kinase family; specifically acts on 'Ser-473' of AKT1, 'Ser-660' of PRKCB isoform beta-II and 'Ser-657' of PRKCA. Akt regulates the balance between cell survival and apoptosis through a cascade that primarily alters the function of transcription factors that regulate pro- and antiapoptotic genes. Dephosphorylation of 'Ser-473' of Akt triggers apoptosis and decreases cell proliferation. Also controls the phosphorylation of AKT3. Dephosphorylates STK4 on 'Thr-387' leading to STK4 activation and apoptosis. Dephosphorylates RPS6KB1 and is involved in regulation of cap-dependent translation. Inhibits cancer cell proliferation and may act as a tumor suppressor. Dephosphorylation of PRKCA and PRKCB leads to their destabilization and degradation. Dephosphorylates RAF1 inhibiting its kinase activity.

References:

[1]. Meng Qiao, et al. Mst1 is an interacting protein that mediates PHLPPs' induced apoptosis. Mol Cell. 2010 May 28;38(4):512-23. [Content Brief]

[2]. Tianyan Gao, et al. The phosphatase PHLPP controls the cellular levels of protein kinase C. J Biol Chem. 2008 Mar 7;283(10):6300-11. [Content Brief]

[3]. J Liu, et al. Loss of PHLPP expression in colon cancer: role in proliferation and tumorigenesis. Oncogene. 2009 Feb 19;28(7):994-1004. [Content Brief]

[4]. Jianyu Liu, et al. PHLPP-mediated dephosphorylation of S6K1 inhibits protein translation and cell growth. Mol Cell Biol. 2011 Dec;31(24):4917-27. [Content Brief]

[5]. John Brognard, et al. PHLPP and a second isoform, PHLPP2, differentially attenuate the amplitude of Akt signaling by regulating distinct Akt isoforms. Mol Cell. 2007 Mar 23;25(6):917-31. [Content Brief]

[6]. Xin Li, et al. PHLPP is a negative regulator of RAF1, which reduces colorectal cancer cell motility and prevents tumor progression in mice. Gastroenterology. 2014 May;146(5):1301-12.e1-10. [Content Brief]

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