Difference between revisions of "Phosphatase Subfamily Slingshot"
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=== Domain === | === 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 (numbering from human SSH1). | + | 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 |
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>. | 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>. | ||
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=== Function === | === Function === | ||
Revision as of 15:35, 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 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].
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 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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