Difference between revisions of "Phosphatase Subfamily PHLPP"
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=== Functions === | === Functions === | ||
| − | + | The PHLPP subfamily dephosphorylates kinases of AGC group at serines in hydrophobic motif. | |
| − | The PHLPP subfamily also dephosphorylates PKC at Ser-660 of human PKC-beta <cite>Gao08</cite>. The position Ser-660 located in hydrophobic motif is conserved across metazoa (replaced by Thr in sea urchin) (see [http://kinase.com/web/current/kinbase/genes/Subfamily/PKCa/alignment/protein/view KinBase]). | + | * PHLPP1 and PHLPP2 dephosphorylates and inactivates kinases of AKT/PKB family at Ser-473 of human AKT1 <cite>Gao05, Brognard07</cite>. PHLPP1 prefers to dephosphorylate AKT2 and PHLPP2 prefers AKT3 <cite>Brognard07</cite>. 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 [http://kinase.com/web/current/kinbase/genes/Family/Akt/alignment/protein/view alignment in KinBase]). |
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| + | * The PHLPP subfamily also dephosphorylates PKC at Ser-660 of human PKC-beta <cite>Gao08</cite>. The position Ser-660 located in hydrophobic motif is conserved across metazoa (replaced by Thr in sea urchin) (see [http://kinase.com/web/current/kinbase/genes/Subfamily/PKCa/alignment/protein/view KinBase]). | ||
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| + | * The PHLPP subfamily also dephosphorylates S6 kinase <cite>Liu11</cite>. | ||
PHLPP1 and PHLPP2 are implicated in different kinds of cancers, such as colon cancer <cite>Liu09</cite>, hypopharyngeal squamous cell carcinomas <cite>Zhou15</cite>. | PHLPP1 and PHLPP2 are implicated in different kinds of cancers, such as colon cancer <cite>Liu09</cite>, hypopharyngeal squamous cell carcinomas <cite>Zhou15</cite>. | ||
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#Gao08 pmid=18162466 | #Gao08 pmid=18162466 | ||
#Liu09 pmid=19079341 | #Liu09 pmid=19079341 | ||
| + | #Liu11 pmid=21986499 | ||
#Zhou15 pmid=25793736 | #Zhou15 pmid=25793736 | ||
</biblio> | </biblio> | ||
Revision as of 02:04, 26 March 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.
Domain
The PHLPP subfamily has a N-terminal PH domain, 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].
PHLPP1 and PHLPP2 are implicated in different kinds of cancers, such as colon cancer [5], hypopharyngeal squamous cell carcinomas [6].
References
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Error fetching PMID 17386267:
Error fetching PMID 18162466:
Error fetching PMID 19079341:
Error fetching PMID 21986499:
Error fetching PMID 25793736:
Error fetching PMID 17386267:
Error fetching PMID 18162466:
Error fetching PMID 19079341:
Error fetching PMID 21986499:
Error fetching PMID 25793736:
- Error fetching PMID 15808505:
- Error fetching PMID 17386267:
- Error fetching PMID 18162466:
- Error fetching PMID 21986499:
- Error fetching PMID 19079341:
- Error fetching PMID 25793736:
