Difference between revisions of "Phosphatase Subfamily DSP15"
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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_DSP15|Subfamily DSP15]] | [[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Fold_CC1|Fold CC1]]: [[Phosphatase_Superfamily_CC1|Superfamily CC1]]: [[Phosphatase_Family_DSP|Family DSP]]: [[Phosphatase_Subfamily_DSP15|Subfamily DSP15]] | ||
| − | summary | + | summary... |
=== Evolution === | === Evolution === | ||
| Line 8: | Line 8: | ||
=== Domain === | === Domain === | ||
| − | DSP15 has a N-terminal myristoylation site and a phosphatase domain. | + | DSP15 has a N-terminal [http://en.wikipedia.org/wiki/Myristoylation myristoylation] site and a phosphatase domain. The two members in human genome DUSP15 and DUSP22 are myristoylated at Gly-2. The myristoylation site targets the protein to plasma memrane. Mutation of the myristoylation site Gly-2 of DUSP15 abrogated membrane location <cite>Alonso04</cite>. |
=== Functions === | === Functions === | ||
| Line 14: | Line 14: | ||
====== DUSP15 (VHY) ====== | ====== DUSP15 (VHY) ====== | ||
| + | Human DUSP15 is specifically expressed in testis <cite> Alonso04</cite> (also see [http://www.gtexportal.org/home/gene/DUSP15 GTEx portal]). However, DUSP15 has also been reported to be transcriptionally regulated during [http://en.wikipedia.org/wiki/Oligodendrocyte oligodendrocyte] differentiation and in [http://en.wikipedia.org/wiki/Multiple_sclerosis multiple sclerosis] lesions, in which DUSP15 dephosphorylates PDGFR-beta and SNX6 <cite>Schmidt12</cite>. | ||
| + | |||
| + | ====== DUSP22 (VHX/JKAP/JSP1/LMW-DSP2) ====== | ||
| + | Different from DUSP15, human DUSP22 is expressed in various tissues (see [http://www.gtexportal.org/home/gene/DUSP22 GTEx portal]). | ||
| + | |||
| + | DUSP22 localizes in the actin filament-enriched region. Expression of DUSP22 reduced cell migration, whereas a DUSP22 mutant lacking catalytic activity promoted cell motility. DUSP22 dephosphorylates tyrosines 397, 576, and 577 of focal adhesion kinase (FAK) <cite>Li10</cite>. DUSP22 also dephosphorylates Ser-118 of estrogen receptor-alpha (ER-alpha) therefore regulating ER-alpha-mediated signaling <cite>Sekine07</cite>. | ||
| + | |||
| + | Unexpectedly, DUSP22 is a positive rather than negative regulatory of JNK pathway. It did not interact with or dephosphorylate JNK in vitro, suggesting that DUSP22 exerts its effect on JNK in an indirect manner <cite>Shen01, Chen02</cite>. | ||
| + | |||
| + | DUSP22 may have other functions. It inhibits (may or may not by directly dephospho rylation) PKA activity and thereby determines TAU phosphorylation status and CREB signaling <cite>Sanchez-Mut14</cite>. | ||
| + | It also acts as a negative regulator (may or may not by directly dephospho rylation) of the IL-6/LIF/STAT3-mediated signaling pathway <cite>Sekine06</cite>. | ||
| + | |||
| + | DUSP22 may represent a tumor-suppressor gene, since its loss may contribute to the pathogenesis of cutaneous anaplastic large-cell lymphomas (ALCLs) according to clinic cases <cite>Csikesz13</cite>. | ||
=== References === | === References === | ||
<biblio> | <biblio> | ||
| − | + | #Alonso04 pmid=15138252 | |
| + | #Chen02 pmid=12138158 | ||
| + | #Csikesz13 pmid=23337887 | ||
| + | #Li10 pmid=20018849 | ||
| + | #Sanchez-Mut14 pmid=24436131 | ||
| + | #Schmidt12 pmid=22792334 | ||
| + | #Sekine06 pmid=16636663 | ||
| + | #Sekine07 pmid=17384676 | ||
| + | #Shen01 pmid=11717427 | ||
</biblio> | </biblio> | ||
Revision as of 04:59, 3 March 2015
Phosphatase Classification: Fold CC1: Superfamily CC1: Family DSP: Subfamily DSP15
summary...
Evolution
Pending..
Domain
DSP15 has a N-terminal myristoylation site and a phosphatase domain. The two members in human genome DUSP15 and DUSP22 are myristoylated at Gly-2. The myristoylation site targets the protein to plasma memrane. Mutation of the myristoylation site Gly-2 of DUSP15 abrogated membrane location [1].
Functions
Two human genes belong to this subfamily: DUSP15 and DUSP22.
DUSP15 (VHY)
Human DUSP15 is specifically expressed in testis [1] (also see GTEx portal). However, DUSP15 has also been reported to be transcriptionally regulated during oligodendrocyte differentiation and in multiple sclerosis lesions, in which DUSP15 dephosphorylates PDGFR-beta and SNX6 [2].
DUSP22 (VHX/JKAP/JSP1/LMW-DSP2)
Different from DUSP15, human DUSP22 is expressed in various tissues (see GTEx portal).
DUSP22 localizes in the actin filament-enriched region. Expression of DUSP22 reduced cell migration, whereas a DUSP22 mutant lacking catalytic activity promoted cell motility. DUSP22 dephosphorylates tyrosines 397, 576, and 577 of focal adhesion kinase (FAK) [3]. DUSP22 also dephosphorylates Ser-118 of estrogen receptor-alpha (ER-alpha) therefore regulating ER-alpha-mediated signaling [4].
Unexpectedly, DUSP22 is a positive rather than negative regulatory of JNK pathway. It did not interact with or dephosphorylate JNK in vitro, suggesting that DUSP22 exerts its effect on JNK in an indirect manner [5, 6].
DUSP22 may have other functions. It inhibits (may or may not by directly dephospho rylation) PKA activity and thereby determines TAU phosphorylation status and CREB signaling [7]. It also acts as a negative regulator (may or may not by directly dephospho rylation) of the IL-6/LIF/STAT3-mediated signaling pathway [8].
DUSP22 may represent a tumor-suppressor gene, since its loss may contribute to the pathogenesis of cutaneous anaplastic large-cell lymphomas (ALCLs) according to clinic cases [9].
References
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Error fetching PMID 17384676:
Error fetching PMID 11717427:
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- Error fetching PMID 22792334:
- Error fetching PMID 20018849:
- Error fetching PMID 17384676:
- Error fetching PMID 11717427:
- Error fetching PMID 12138158:
- Error fetching PMID 24436131:
- Error fetching PMID 16636663:
- Error fetching PMID 23337887:
