Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

PH Domain Leucine-Rich Repeat Protein Phosphatase (PHLPP)

  • Agnieszka T. Grzechnik
  • Alexandra C. NewtonEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101823


Historical Background

In 1999, Shimuzu et al. identified a novel transcript that oscillated in a circadian-dependent manner in the rat suprachiasmatic nucleus (SCN), a bundle of neurons in the brain responsible for controlling the mammalian circadian clock (Shimizu et al. 1999). Thus, they named this gene product SCN circadian oscillatory protein (SCOP), but the function of the protein encoded by this gene was shrouded in mystery. Six years later, Newton and colleagues identified this same gene in a rational search for a serine/threonine phosphatase responsible for dephosphorylating and inactivating the pro-survival kinase, Akt (Gao et al. 2005). Upon agonist stimulation, Akt is recruited to the plasma membrane by its phosphoinositide-sensing pleckstrin homology (PH) domain, where it becomes phosphorylated by another PH domain-containing kinase, the phosphoinositide-dependent kinase-1 (PDK-1). Hypothesizing that a phosphatase that...

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© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Biomedical Sciences Graduate ProgramUniversity of California San DiegoLa JollaUSA
  2. 2.Department of PharmacologyUniversity of California San DiegoSan DiegoUSA