Pleckstrin homology domain leucine-rich repeat protein phosphatase (PHLPP): A new player in cell signaling

Noel A. Warfel, Alexandra C. Newton

Research output: Contribution to journalShort surveypeer-review

61 Scopus citations


Precise balance between phosphorylation, catalyzed by protein kinases, and dephosphorylation, catalyzed by protein phosphatases, is essential for cellular homeostasis. Deregulation of this balance leads to pathophysiological states that drive diseases such as cancer, heart disease, and diabetes. The recent discovery of the PHLPP (pleckstrin homology domain leucinerich repeat protein phosphatase) family of Ser/Thr phosphatases adds a new player to the cast of phosphate-controlling enzymes in cell signaling. PHLPP isozymes catalyze the dephosphorylation of a conserved regulatory motif, the hydrophobic motif, on the AGC kinases Akt, PKC, and S6 kinase, as well as an inhibitory site on the kinase Mst1, to inhibit cellular proliferation and induce apoptosis. The frequent deletion of PHLPP in cancer, coupled with the development of prostate tumors in mice lacking PHLPP1, identifies PHLPP as a novel tumor suppressor. This minireview discusses the structure, function, and regulation of PHLPP, with particular focus on its role in disease.

Original languageEnglish (US)
Pages (from-to)3610-3616
Number of pages7
JournalJournal of Biological Chemistry
Issue number6
StatePublished - Feb 3 2012
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'Pleckstrin homology domain leucine-rich repeat protein phosphatase (PHLPP): A new player in cell signaling'. Together they form a unique fingerprint.

Cite this