Difference between revisions of "Phosphatase Subfamily PHLPP"
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=== Domain === | === Domain === | ||
| − | The PHLPP subfamily has a N-terminal PH domain, leucine rich repeats, phosphatase domain, and a C-terminal PDZ-domain binding motif. | + | The PHLPP subfamily has a N-terminal PH domain, a various number of leucine rich repeats, phosphatase domain, and a C-terminal PDZ-domain binding motif. |
=== Functions === | === Functions === | ||
Revision as of 22:51, 18 June 2015
Phosphatase Classification: Fold PPM (PP2C): Superfamily PPM (PP2C): Family PPM (PP2C): Subfamily PHLPP (PH domain and leucine rich repeat protein phosphatase)
PHLPP stands for PH domain and leucine rich repeat protein phosphatase.
Evolution
The PHLPP subfamily is found across bilateria. Human has two members, PHLPP1/SCOP andPHLPP2, which most likely originated from vertebrate whole genome duplication. Human PHLPPs have a PH domain, which is also found in other deuterostome PHLPPs, as well as lophotrochozoa PHLPPs, by BLASTing human PH domain against NR database. However, it is absent from ecdysozoa (e.g. Drosophila and Caenorhabditis). Since both ecdysozoa and lophotrochozoa are protostomes, it is most probably that the PHLPP in bilateral ancestor had PH domain, but it was lost in ecdysozoa.
Domain
The PHLPP subfamily has a N-terminal PH domain, a various number of leucine rich repeats, phosphatase domain, and a C-terminal PDZ-domain binding motif.
Functions
The PHLPP subfamily dephosphorylates kinases of AGC group at serines in hydrophobic motif.
- PHLPP1 and PHLPP2 dephosphorylates and inactivates kinases of AKT/PKB family at Ser-473 of human AKT1 [1, 2]. PHLPP1 prefers to dephosphorylate AKT2 and PHLPP2 prefers AKT3 [2]. The position Ser-473 located in hydrophobic motif is conserved across bilateria and among the three human members. It is also found in one sponge AKT, but not all three sponge AKTs (see alignment in KinBase).
- The PHLPP subfamily also dephosphorylates PKC at Ser-660 of human PKC-beta [3]. The position Ser-660 located in hydrophobic motif is conserved across metazoa (replaced by Thr in sea urchin) (see KinBase).
- The PHLPP subfamily also dephosphorylates S6 kinase [4].
Loss of PHLPP can increase the level of phosphorylated Survivin, a member of the inhibitor of apoptosis (IAP) family, in gallbladder carcinoma (GBC) cells [5]. But, it is unclear whether PHLPP directly dephosphorylates Survivin.
PHLPP1 and PHLPP2 are implicated in different kinds of cancers, such as colon cancer [6], hypopharyngeal squamous cell carcinomas [7].
References
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