Difference between revisions of "Phosphatase Subfamily DSP10"

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[[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Fold_CC1|Fold CC1]]:  [[Phosphatase_Superfamily_CC1|Superfamily CC1]]: [[Phosphatase_Family_DSP|Family DSP]]: [[Phosphatase_Subfamily_ DSP10 |Subfamily DSP10 (MKP5)]]
 
[[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Fold_CC1|Fold CC1]]:  [[Phosphatase_Superfamily_CC1|Superfamily CC1]]: [[Phosphatase_Family_DSP|Family DSP]]: [[Phosphatase_Subfamily_ DSP10 |Subfamily DSP10 (MKP5)]]
  
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STYXL1 (MK-STYX) is a pseudophosphatase (catalytically inactive) conserved in metazoan but lost in ecdysozoan. Two binding partners have been known so far: phosphatase PTPMT1 and a Ras signaling regulator G3BP1.
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DSP10 selectively dephosphorylates p38 and JNK. It is conserved across holozoan but lost in nematodes.
  
 
=== Evolution ===
 
=== Evolution ===
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STYXL1 is found in [[metazoa]] but lost in [[ecdysozoa]] (arthropoda and nematoda). It is usually a copy per genome.
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DSP10 (MKP5) subfamily is found in most holozoan except nematodes. DSP10 is usually one copy per genome, e.g. DUSP10 in human.
  
 
=== Domain ===
 
=== Domain ===
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STYXL1 has two domains, N-terminal rhodanese domain and C-terminal the phosphatase domain.  
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DSP10 has two domains: rhodanese domain and phosphatase domain. Rhodanese domain can bind to kinases <cite>Tao07</cite>.  
  
 
=== Function ===
 
=== Function ===
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STYXL1 is expressed in most tissues (see [http://www.gtexportal.org/home/gene/STYXL1 GTEx data]).
 
  
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STYXL1 physically and genetically interacts with the mitochondrial phosphatase PTPMT1, and suppresses PTPMT1 catalytic activity. STYXL1 knockdown induces robust chemoresistance to multiple cytotoxic death-inducing agents.  Loss of STYXL1 blocks cytochrome c release, a critical and rate-limiting step in apoptosis. knockdown of PTPMT1 resensitizes STYXL1 knockdown cells to chemotherapeutics and restores the ability to release cytochrome c. Thus, a model has been proposed that MK-STYX controls apoptosis by negatively regulating PTPMT1 <cite> Niemi11, Niemi14</cite>.  
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DUSP10 is phosphatase specific for p38 and SAPK/JNK. It binds to p38 and SAPK/JNK, but not to MAPK/ERK, and inactivates p38 and SAPK/JNK, but not MAPK/ERK. p38 is a preferred substrate. It is present evenly in both the cytoplasm and the nucleus. DUSP10 is widely expressed in various tissues and organs, and its expression in cultured cells is elevated by stress stimuli <cite>Tanoue99, Theodosiou99, Jeong06</cite>.
  
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STYXL1 also interacts with G3BP-1 (Ras-GTPase activating protein SH3 domain binding protein-1), a key component of stress granules. G3BP1 is an RNA-binding protein with endoribonuclease activity that is recruited to 'stress granules' after stress stimuli. Stress granules are large subcellular structures that serve as sites of mRNA sorting, in which untranslated mRNAs accumulate. Active mutant STYXL1 (active) has opposite effects to wild-type STYKL1 (inactive). The mutant STYXL1 (active) induces stress granules and dephosphorylates G3BP-1. <cite>Hinton10, Barr13</cite>.
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On the other hand, it has been reported that DUSP10 interacts with ERK, retains it in the cytoplasm, suppresses its activation and downregulates ERK-dependent transcription <cite>Nomura12</cite>.
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Human DUSP10 is frequently upregulated in colorectal cancer (CRC). Certain mutations in DUSP10 correlate with the incidence of CRC.
  
 
=== References ===
 
=== References ===
 
<biblio>
 
<biblio>
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#Jeong06 pmid=16806267
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#Nomura12 pmid=22711061
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#Tanoue99 pmid=10391943
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#Tao07 pmid=17400920
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#Theodosiou99 pmid=10597297
 
</biblio>
 
</biblio>

Revision as of 00:30, 4 March 2015

Phosphatase Classification: Fold CC1: Superfamily CC1: Family DSP: Subfamily DSP10 (MKP5)

DSP10 selectively dephosphorylates p38 and JNK. It is conserved across holozoan but lost in nematodes.

Evolution

DSP10 (MKP5) subfamily is found in most holozoan except nematodes. DSP10 is usually one copy per genome, e.g. DUSP10 in human.

Domain

DSP10 has two domains: rhodanese domain and phosphatase domain. Rhodanese domain can bind to kinases [1].

Function

DUSP10 is phosphatase specific for p38 and SAPK/JNK. It binds to p38 and SAPK/JNK, but not to MAPK/ERK, and inactivates p38 and SAPK/JNK, but not MAPK/ERK. p38 is a preferred substrate. It is present evenly in both the cytoplasm and the nucleus. DUSP10 is widely expressed in various tissues and organs, and its expression in cultured cells is elevated by stress stimuli [2, 3, 4].

On the other hand, it has been reported that DUSP10 interacts with ERK, retains it in the cytoplasm, suppresses its activation and downregulates ERK-dependent transcription [5].

Human DUSP10 is frequently upregulated in colorectal cancer (CRC). Certain mutations in DUSP10 correlate with the incidence of CRC.

References

  1. Tao X and Tong L. Crystal structure of the MAP kinase binding domain and the catalytic domain of human MKP5. Protein Sci. 2007 May;16(5):880-6. DOI:10.1110/ps.062712807 | PubMed ID:17400920 | HubMed [Tao07]
  2. Tanoue T, Moriguchi T, and Nishida E. Molecular cloning and characterization of a novel dual specificity phosphatase, MKP-5. J Biol Chem. 1999 Jul 9;274(28):19949-56. DOI:10.1074/jbc.274.28.19949 | PubMed ID:10391943 | HubMed [Tanoue99]
  3. Theodosiou A, Smith A, Gillieron C, Arkinstall S, and Ashworth A. MKP5, a new member of the MAP kinase phosphatase family, which selectively dephosphorylates stress-activated kinases. Oncogene. 1999 Nov 25;18(50):6981-8. DOI:10.1038/sj.onc.1203185 | PubMed ID:10597297 | HubMed [Theodosiou99]
  4. Jeong DG, Yoon TS, Kim JH, Shim MY, Jung SK, Son JH, Ryu SE, and Kim SJ. Crystal structure of the catalytic domain of human MAP kinase phosphatase 5: structural insight into constitutively active phosphatase. J Mol Biol. 2006 Jul 28;360(5):946-55. DOI:10.1016/j.jmb.2006.05.059 | PubMed ID:16806267 | HubMed [Jeong06]
  5. Nomura M, Shiiba K, Katagiri C, Kasugai I, Masuda K, Sato I, Sato M, Kakugawa Y, Nomura E, Hayashi K, Nakamura Y, Nagata T, Otsuka T, Katakura R, Yamashita Y, Sato M, Tanuma N, and Shima H. Novel function of MKP-5/DUSP10, a phosphatase of stress-activated kinases, on ERK-dependent gene expression, and upregulation of its gene expression in colon carcinomas. Oncol Rep. 2012 Sep;28(3):931-6. DOI:10.3892/or.2012.1862 | PubMed ID:22711061 | HubMed [Nomura12]
All Medline abstracts: PubMed | HubMed
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