PHLPP

PH domain and leucine-rich repeat protein phosphatase
Identifiers
SymbolPHLPP
Alt. symbolsPHLPP1, PLEKHE1
NCBI gene23239
HGNC20610
OMIM609396
RefSeqXM_166290
UniProtO60346
Other data
EC number3.1.3.16
LocusChr. 18 q21.32
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StructuresSwiss-model
DomainsInterPro
PH domain and leucine rich repeat protein phosphatase-like
Identifiers
SymbolPHLPPL
Alt. symbolsPHLPP2
NCBI gene23035
HGNC29149
OMIM611066
RefSeqNM_015020
UniProtQ6ZVD8
Other data
EC number3.1.3.16
LocusChr. 16 q22.2
Search for
StructuresSwiss-model
DomainsInterPro

The PHLPP isoforms (PH domain and Leucine rich repeat Protein Phosphatases) are a pair of protein phosphatases, PHLPP1 and PHLPP2, that are important regulators of Akt serine-threonine kinases (Akt1, Akt2, Akt3) and conventional/novel protein kinase C (PKC) isoforms. PHLPP may act as a tumor suppressor in several types of cancer due to its ability to block growth factor-induced signaling in cancer cells.[1]

PHLPP dephosphorylates Ser-473 (the hydrophobic motif) in Akt, thus partially inactivating the kinase.[2]

In addition, PHLPP dephosphorylates conventional and novel members of the protein kinase C family at their hydrophobic motifs, corresponding to Ser-660 in PKCβII.[3]

  1. ^ Brognard J, Newton AC (August 2008). "PHLiPPing the Switch on Akt and Protein Kinase C Signaling". Trends Endocrinol. Metab. 19 (6): 223–30. doi:10.1016/j.tem.2008.04.001. PMC 2963565. PMID 18511290.
  2. ^ Gao T, Furnari F, Newton AC (April 2005). "PHLPP: a phosphatase that directly dephosphorylates Akt, promotes apoptosis, and suppresses tumor growth". Mol. Cell. 18 (1): 13–24. doi:10.1016/j.molcel.2005.03.008. PMID 15808505.
  3. ^ Gao T, Brognard J, Newton AC (March 2008). "The phosphatase PHLPP controls the cellular levels of protein kinase C". J. Biol. Chem. 283 (10): 6300–11. doi:10.1074/jbc.M707319200. PMID 18162466.