Difference between revisions of "Phosphatase Subfamily Slingshot"
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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_Slingshot|Subfamily Slingshot]] | [[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Fold_CC1|Fold CC1]]: [[Phosphatase_Superfamily_CC1|Superfamily CC1]]: [[Phosphatase_Family_DSP|Family DSP]]: [[Phosphatase_Subfamily_Slingshot|Subfamily Slingshot]] | ||
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=== Domain === | === Domain === | ||
| − | Slingshot has | + | Slingshot has three domains: A domain (1-124), B domain (125-308), phosphatase domain (309-450) and Serine-enriched region close to C-terminus (positioned by human SSH1). |
| + | A domain is required for the F-actin-mediated activation of SSH1 and therefore may mediate slingshot binding to actin. F-actin increased the cofilin-phosphatase activity of SSH1 more than 1200-fold. B domain and phosphatase domain are indispensable for phosphorylated-cofilin (P-cofilin) binding. The phosphatase domain alone is sufficient for the phosphatase activity toward p-nitrophenyl phosphate (pNPP), indicating that the SSH-N domain is not essential for the basal phosphatase activity of SSH1 <cite>Kurita08</cite>. Besides, motifs LHKACE (amino acids 185–190) in the B domain and LKRSHS (amino acids 973–978) in the S domain of SSH1 may also contribute to F-actin binding <cite>Yamamoto06</cite>. | ||
| + | |||
| + | Note: As annotated by Pfam, there is a DEK C terminal domain from 251 to 303, which is part of B domain. | ||
=== Function === | === Function === | ||
| + | Slingshots dephosphorylate [http://en.wikipedia.org/wiki/Cofilin cofilin], a ubiquitous actin-binding factor required for the reorganization of actin filaments, in Drosophila and human <cite>Niwa02</cite> (see [http://www.nature.com/nrm/journal/v14/n7/fig_tab/nrm3609_F6.html here] for cofilin function). In human, there are three members in slingshot subfamily. They are significantly different in subcellular distribution, F-actin-binding activity, specific phosphatase activity and expression patterns, which suggests that they have related but distinct functions in various cellular and developmental events <cite>Ohta02</cite>. | ||
| + | |||
| + | In addition to substrate cofilin, [http://en.wikipedia.org/wiki/Coronin Coronin 1B] has been proposed to be slingshot's substrate <cite>Cai07</cite>. | ||
| + | === Regulation === | ||
| + | Slingshot is regulated by protein kinase D (PKD), which phosphorylates serines 937 and 978 and therefore regulates human SSH1 subcellular localization by binding of 14-3-3 proteins <cite>Peterburs09</cite>. PKD also phosphorylates serine 402 that impedes phosphatase activity of human SSH1 <cite>Barisic11</cite>. 14-3-3zeta/tau heterodimers regulate Slingshot activity in migrating keratinocytes <cite>Kligys09</cite>. SSH1L is activated by its release from a regulatory complex with 14-3-3zeta protein through the redox-mediated oxidation of 14-3-3zeta <cite>Kim09</cite>. | ||
=== References === | === References === | ||
| + | <biblio> | ||
| + | #Cai07 pmid=17350576 | ||
| + | #Kim09 pmid=19339277 | ||
| + | #Kligys09 pmid=19371722 | ||
| + | #Kurita08 pmid=18809681 | ||
| + | #Niwa02 pmid=11832213 | ||
| + | #Ohta02 pmid=14531860 | ||
| + | #Peterburs09 pmid=19567672 | ||
| + | #Barisic11 pmid=21525957 | ||
| + | #Yamamoto06 pmid=16513117 | ||
| + | </biblio> | ||
Revision as of 02:14, 27 February 2015
Phosphatase Classification: Fold CC1: Superfamily CC1: Family DSP: Subfamily Slingshot
(summary)
Evolution
Slingshot is found across holozoan, but absent from C. elegans as well as other nematodes.
Domain
Slingshot has three domains: A domain (1-124), B domain (125-308), phosphatase domain (309-450) and Serine-enriched region close to C-terminus (positioned by human SSH1). A domain is required for the F-actin-mediated activation of SSH1 and therefore may mediate slingshot binding to actin. F-actin increased the cofilin-phosphatase activity of SSH1 more than 1200-fold. B domain and phosphatase domain are indispensable for phosphorylated-cofilin (P-cofilin) binding. The phosphatase domain alone is sufficient for the phosphatase activity toward p-nitrophenyl phosphate (pNPP), indicating that the SSH-N domain is not essential for the basal phosphatase activity of SSH1 [1]. Besides, motifs LHKACE (amino acids 185–190) in the B domain and LKRSHS (amino acids 973–978) in the S domain of SSH1 may also contribute to F-actin binding [2].
Note: As annotated by Pfam, there is a DEK C terminal domain from 251 to 303, which is part of B domain.
Function
Slingshots dephosphorylate cofilin, a ubiquitous actin-binding factor required for the reorganization of actin filaments, in Drosophila and human [3] (see here for cofilin function). In human, there are three members in slingshot subfamily. They are significantly different in subcellular distribution, F-actin-binding activity, specific phosphatase activity and expression patterns, which suggests that they have related but distinct functions in various cellular and developmental events [4].
In addition to substrate cofilin, Coronin 1B has been proposed to be slingshot's substrate [5].
Regulation
Slingshot is regulated by protein kinase D (PKD), which phosphorylates serines 937 and 978 and therefore regulates human SSH1 subcellular localization by binding of 14-3-3 proteins [6]. PKD also phosphorylates serine 402 that impedes phosphatase activity of human SSH1 [7]. 14-3-3zeta/tau heterodimers regulate Slingshot activity in migrating keratinocytes [8]. SSH1L is activated by its release from a regulatory complex with 14-3-3zeta protein through the redox-mediated oxidation of 14-3-3zeta [9].
References
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