Difference between revisions of "Phosphatase Subfamily Slingshot"
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=== Domain === | === Domain === | ||
| − | Slingshot has three domains defined experimentally: A domain (1-124), B domain (125-308), phosphatase domain (309-450) and Serine-enriched region close to C-terminus (numbering from human SSH1) <cite>Kurita08</cite>. The B domain includes the Pfam domain DEK_C | + | Slingshot has three domains defined experimentally: A domain (1-124), B domain (125-308), phosphatase domain (309-450) and Serine-enriched region close to C-terminus (numbering from human SSH1) <cite>Kurita08</cite>. The B domain includes the Pfam domain DEK_C. The 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. The 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) <cite>Kurita08</cite>. The motifs LHKACE (AA 185–190) in the B domain and LKRSHS (AA 973–978) in the S domain of SSH1 may also contribute to F-actin binding <cite>Yamamoto06</cite>. |
| − | 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) | + | |
=== Function === | === Function === | ||
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=== Regulation === | === Regulation === | ||
| − | Slingshot is regulated by protein kinase D (PKD), which phosphorylates serines 937 and 978 and | + | Slingshot is regulated by protein kinase D (PKD), which phosphorylates serines 937 and 978 and regulates human SSH1 subcellular localization by binding of 14-3-3 proteins <cite>Peterburs09</cite>. PKD also phosphorylates serine 402 to inhibit phosphatase activity <cite>Barisic11</cite>. 14-3-3zeta/tau heterodimers regulate Slingshot activity in migrating keratinocytes <cite>Kligys09</cite>. SSH1 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 === | ||
Revision as of 15:39, 22 March 2017
Phosphatase Classification: Fold CC1: Superfamily CC1: Family DSP: Subfamily Slingshot
Slingshot regulates cofilin phosphorylation with LIMK kinase subfamily.
Evolution
Slingshot is found across holozoa, but absent from nematodes.
Domain
Slingshot has three domains defined experimentally: A domain (1-124), B domain (125-308), phosphatase domain (309-450) and Serine-enriched region close to C-terminus (numbering from human SSH1) [1]. The B domain includes the Pfam domain DEK_C. The 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. The 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) [1]. The motifs LHKACE (AA 185–190) in the B domain and LKRSHS (AA 973–978) in the S domain of SSH1 may also contribute to F-actin binding [2].
Function
Slingshot dephosphorylates cofilin, a ubiquitous actin-binding factor required for the reorganization of actin filaments, in Drosophila and human [3] (see here for cofilin function). The three human slingshot genes are significantly different in subcellular distribution, actin-binding activity, phosphatase activity and expression patterns [4]. Coronin 1B has also been proposed to be a slingshot substrate [5].
Regulation
Slingshot is regulated by protein kinase D (PKD), which phosphorylates serines 937 and 978 and regulates human SSH1 subcellular localization by binding of 14-3-3 proteins [6]. PKD also phosphorylates serine 402 to inhibit phosphatase activity [7]. 14-3-3zeta/tau heterodimers regulate Slingshot activity in migrating keratinocytes [8]. SSH1 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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