SSH1

Summary

Gene Symbol: SSH1
Description: slingshot protein phosphatase 1
Alias: SSH1L, protein phosphatase Slingshot homolog 1, SSH-like protein 1, hSSH-1L, slingshot homolog 1
Species: human
Products:     SSH1

Top Publications

  1. Ohta Y, Kousaka K, Nagata Ohashi K, Ohashi K, Muramoto A, Shima Y, et al. Differential activities, subcellular distribution and tissue expression patterns of three members of Slingshot family phosphatases that dephosphorylate cofilin. Genes Cells. 2003;8:811-24 pubmed
  2. Nishita M, Wang Y, Tomizawa C, Suzuki A, Niwa R, Uemura T, et al. Phosphoinositide 3-kinase-mediated activation of cofilin phosphatase Slingshot and its role for insulin-induced membrane protrusion. J Biol Chem. 2004;279:7193-8 pubmed
    ..Here we show that insulin stimulates the phosphatase activity of Slingshot-1L (SSH1L) and cofilin dephosphorylation in cultured cells, in a manner dependent on phosphoinositide 3-kinase (PI3K) ..
  3. Nagata Ohashi K, Ohta Y, Goto K, Chiba S, Mori R, Nishita M, et al. A pathway of neuregulin-induced activation of cofilin-phosphatase Slingshot and cofilin in lamellipodia. J Cell Biol. 2004;165:465-71 pubmed
    ..Cofilin is inactivated by phosphorylation at Ser-3 and reactivated by cofilin-phosphatase Slingshot-1L (SSH1L). Little is known of signaling mechanisms of cofilin activation and how this activation is spatially regulated...
  4. Cai L, Marshall T, Uetrecht A, Schafer D, Bear J. Coronin 1B coordinates Arp2/3 complex and cofilin activities at the leading edge. Cell. 2007;128:915-29 pubmed
    ..We report that Coronin 1B interacts simultaneously with Arp2/3 complex and Slingshot (SSH1L) phosphatase, two regulators of actin filament formation and turnover, respectively...
  5. Nishita M, Tomizawa C, Yamamoto M, Horita Y, Ohashi K, Mizuno K. Spatial and temporal regulation of cofilin activity by LIM kinase and Slingshot is critical for directional cell migration. J Cell Biol. 2005;171:349-59 pubmed
    ..In this study, we show that cofilin activity is temporally and spatially regulated by LIMK1 and SSH1L in chemokine-stimulated Jurkat T cells...
  6. Niwa R, Nagata Ohashi K, Takeichi M, Mizuno K, Uemura T. Control of actin reorganization by Slingshot, a family of phosphatases that dephosphorylate ADF/cofilin. Cell. 2002;108:233-46 pubmed
    ..Furthermore, SSH and the hSSHs dephosphorylated P cofilin in cultured cells and in cell-free assays. Our results strongly suggest that the SSH family plays a pivotal role in actin dynamics by reactivating ADF/cofilin in vivo...
  7. Soosairajah J, Maiti S, Wiggan O, Sarmiere P, Moussi N, Sarcevic B, et al. Interplay between components of a novel LIM kinase-slingshot phosphatase complex regulates cofilin. EMBO J. 2005;24:473-86 pubmed
    ..Here we define a novel ADF/cofilin phosphoregulatory complex and suggest a new mechanism for the regulation of ADF/cofilin activity in mediating changes to the actin cytoskeleton. ..
  8. Yamamoto M, Nagata Ohashi K, Ohta Y, Ohashi K, Mizuno K. Identification of multiple actin-binding sites in cofilin-phosphatase Slingshot-1L. FEBS Lett. 2006;580:1789-94 pubmed
    Slingshot-1L (SSH1L) is a phosphatase that specifically dephosphorylates and activates cofilin, an actin-severing and -depolymerizing protein...
  9. Endo M, Ohashi K, Sasaki Y, Goshima Y, Niwa R, Uemura T, et al. Control of growth cone motility and morphology by LIM kinase and Slingshot via phosphorylation and dephosphorylation of cofilin. J Neurosci. 2003;23:2527-37 pubmed
    ..cone motility and morphology and neurite extension by expressing fluorescence protein-labeled cofilin, LIMK1, SSH1, or their mutants in chick dorsal root ganglion (DRG) neurons and then monitoring live images of growth cones by ..

More Information

Publications55

  1. Kaji N, Ohashi K, Shuin M, Niwa R, Uemura T, Mizuno K. Cell cycle-associated changes in Slingshot phosphatase activity and roles in cytokinesis in animal cells. J Biol Chem. 2003;278:33450-5 pubmed
    ..by phosphorylation on Ser-3 by LIM-kinase-1 (LIMK1) and is reactivated by a protein phosphatase Slingshot-1 (SSH1)...
  2. Hsieh Y, Tu H, Pan S, Liou J, Yang C. Anti-metastatic activity of MPT0G211, a novel HDAC6 inhibitor, in human breast cancer cells in vitro and in vivo. Biochim Biophys Acta Mol Cell Res. 2019;1866:992-1003 pubmed publisher
    ..F-actin polymerization by increasing cortactin acetylation and downregulating slingshot protein phosphatase 1 (SSH1) and active cofilin expression. In vivo, MPT0G211 treatment significantly ameliorated TNBC metastasis...
  3. Bielig H, Lautz K, Braun P, Menning M, Machuy N, Brügmann C, et al. The cofilin phosphatase slingshot homolog 1 (SSH1) links NOD1 signaling to actin remodeling. PLoS Pathog. 2014;10:e1004351 pubmed publisher
    ..Here, we identified in a druggable-genome wide siRNA screen the cofilin phosphatase SSH1 as a specific and essential component of the NOD1 pathway...
  4. Woo J, Boggess T, Uhlar C, Wang X, Khan H, Cappos G, et al. RanBP9 at the intersection between cofilin and Aβ pathologies: rescue of neurodegenerative changes by RanBP9 reduction. Cell Death Dis. 2015;6:1676 pubmed publisher
    ..and induction of cofilin-actin pathology require the activation/dephosphorylation of cofilin by Slingshot homolog 1 (SSH1) and cysteine oxidation of cofilin...
  5. Fan C, Song Q, Wang P, Li Y, Yang M, Liu B, et al. Curcumin Protects Against Chronic Stress-induced Dysregulation of Neuroplasticity and Depression-like Behaviors via Suppressing IL-1β Pathway in Rats. Neuroscience. 2018;392:92-106 pubmed publisher
    ..antagonists significantly ameliorated this dysregulation of neuronal structure and biochemical parameters such as SSH1 and phospho-cofilin within the mPFC, as well as the display of depression-like behaviors induced by CUMS exposure...
  6. Woo J, Zhao X, Khan H, Penn C, Wang X, Joly Amado A, et al. Slingshot-Cofilin activation mediates mitochondrial and synaptic dysfunction via Aβ ligation to β1-integrin conformers. Cell Death Differ. 2015;22:921-34 pubmed publisher
    ..1-integrin, resulting in the loss of surface β1-integrin and activation of Cofilin via Slingshot homology-1 (SSH1) activation...
  7. Habeck G, Ebner F, Shimada Kreft H, Kreft S. The yeast ERAD-C ubiquitin ligase Doa10 recognizes an intramembrane degron. J Cell Biol. 2015;209:261-73 pubmed publisher
    ..Sbh2 is part of the trimeric Ssh1 complex involved in protein translocation. Unassembled Sbh2 is rapidly degraded in a Doa10-dependent manner...
  8. Barone E, Mosser S, Fraering P. Inactivation of brain Cofilin-1 by age, Alzheimer's disease and γ-secretase. Biochim Biophys Acta. 2014;1842:2500-9 pubmed
    ..occurring with regard to Cofilin1 and its up-stream regulators Lim kinase-1 (LIMK1) and Slingshot phosphatase-1 (SSH1) in (i) human AD brain, (ii) 1-, 4-, and 10-months old APP/PS1 mice, (iii) wildtype 3-, 8-, 12-, 18- and 26-months ..
  9. Williams H, Ma J, Weiss D, LASSEGUE B, Sutliff R, San Martin A. The cofilin phosphatase slingshot homolog 1 restrains angiotensin II-induced vascular hypertrophy and fibrosis in vivo. Lab Invest. 2019;99:399-410 pubmed publisher
    The dual specificity phosphatase slingshot homolog 1 (SSH1) contributes to actin remodeling by dephosphorylating and activating the actin-severing protein cofilin...
  10. Singla B, Lin H, Ghoshal P, Cherian Shaw M, Csanyi G. PKCδ stimulates macropinocytosis via activation of SSH1-cofilin pathway. Cell Signal. 2019;53:111-121 pubmed publisher
    ..blot analysis demonstrated that phorbol ester and HGF stimulate activation of slingshot phosphatase homolog 1 (SSH1) and induce cofilin Ser-3 dephosphorylation via PKCδ in macrophages...
  11. Liu L, Li J, Zhang L, Zhang F, Zhang R, Chen X, et al. Cofilin phosphorylation is elevated after F-actin disassembly induced by Rac1 depletion. Biofactors. 2015;41:352-9 pubmed publisher
    ..cofilin phosphorylation was aberrantly elevated, corresponding to repression of the phosphatase slingshot1 (SSH1)...
  12. Kubo T, Hirono M, Aikawa T, Kamiya R, Witman G. Reduced tubulin polyglutamylation suppresses flagellar shortness in Chlamydomonas. Mol Biol Cell. 2015;26:2810-22 pubmed publisher
    ..normal; previously it was shown that this shortness can be suppressed by the mutation suppressor of shortness 1 (ssh1) via an unknown mechanism...
  13. Zafar S, Younas N, Sheikh N, Tahir W, Shafiq M, Schmitz M, et al. Cytoskeleton-Associated Risk Modifiers Involved in Early and Rapid Progression of Sporadic Creutzfeldt-Jakob Disease. Mol Neurobiol. 2018;55:4009-4029 pubmed publisher
    ..demonstrated alterations in upstream regulators; LIM kinase isoform 1 (LIMK1), slingshot phosphatase isoform 1 (SSH1), RhoA-associated kinase (Rock2), and amyloid precursor protein (APP) in sporadic Creutzfeldt-Jakob disease MM1 ..
  14. Aggelou H, Chadla P, Nikou S, Karteri S, Maroulis I, Kalofonos H, et al. LIMK/cofilin pathway and Slingshot are implicated in human colorectal cancer progression and chemoresistance. Virchows Arch. 2018;472:727-737 pubmed publisher
    ..We evaluated expression of non-phosphorylated (active) and phosphorylated cofilin, LIMK1, LIMK2, and SSH1 by immunohistochemistry in 143 human CRC samples in relation to clinicopathologic parameters, response of ..
  15. Majumder P, Roy K, Singh B, Jana N, Mukhopadhyay D. Cellular levels of Grb2 and cytoskeleton stability are correlated in a neurodegenerative scenario. Dis Model Mech. 2017;10:655-669 pubmed publisher
    ..cytoskeletal disassembly, in turn blocking the activity of nitrogen oxides and decreasing the expression of slingshot homolog 1 (SSH-1) protein, a potent inducer of cytoskeleton disassembly...
  16. Zhang J, Wang P, He W, Wang F. [Changes in expression of Slingshot protein in hypoxic human intestinal epithelial cell and its relation with barrier function of the cells]. Zhonghua Shao Shang Za Zhi. 2016;32:249-53 pubmed publisher
  17. Yamashiro Y, Papke C, Kim J, Ringuette L, Zhang Q, Liu Z, et al. Abnormal mechanosensing and cofilin activation promote the progression of ascending aortic aneurysms in mice. Sci Signal. 2015;8:ra105 pubmed publisher
    ..depolymerizing factor cofilin was dephosphorylated and thus activated, and at P7, the abundance of slingshot-1 (SSH1) phosphatase, an activator of cofilin, was increased, leading to actin cytoskeletal remodeling...
  18. Maimaiti Y, Maimaitiming M, Li Y, Aibibula S, Ainiwaer A, Aili A, et al. SSH1 expression is associated with gastric cancer progression and predicts a poor prognosis. BMC Gastroenterol. 2018;18:12 pubmed publisher
    Slingshot homolog-1 (SSH1) plays an important role in pathological processes, including in the occurrence and development of tumours...
  19. Ottman R, Levy J, Grizzle W, Chakrabarti R. The other face of miR-17-92a cluster, exhibiting tumor suppressor effects in prostate cancer. Oncotarget. 2016;7:73739-73753 pubmed publisher
    ..of all members of miR-17-92a cluster showed, decreased expression of cell cycle regulatory proteins cyclin D1 and SSH1; and LIMK1 and FGD4 of RhoGTPase signaling pathway...
  20. Xiang Y, Zheng K, Zhong M, Chen J, Wang X, Wang Q, et al. Ubiquitin-proteasome-dependent slingshot 1 downregulation in neuronal cells inactivates cofilin to facilitate HSV-1 replication. Virology. 2014;449:88-95 pubmed publisher
    ..This consistent cofilin inactivation was achieved by the downregulation of slingshot 1 (SSH1). Notably, virus-induced SSH1 downregulation depended on the ubiquitin-proteasome system...
  21. Wang Y, Kuramitsu Y, Kitagawa T, Baron B, Yoshino S, Maehara S, et al. Cofilin-phosphatase slingshot-1L (SSH1L) is over-expressed in pancreatic cancer (PC) and contributes to tumor cell migration. Cancer Lett. 2015;360:171-6 pubmed publisher
    Slingshot-1L (SSH1L), a cofilin-phosphatase, plays a role in actin dynamics and cell migration by reactivating cofilin-1. However, the expression of SSH1L in malignant diseases is poorly understood...
  22. Wang Y, Shibasaki F, Mizuno K. Calcium signal-induced cofilin dephosphorylation is mediated by Slingshot via calcineurin. J Biol Chem. 2005;280:12683-9 pubmed
    ..The Ca2+ ionophore A23187 and Ca2+-mobilizing agonists, ATP and histamine, induced SSH1L activation and cofilin dephosphorylation in cultured cells...
  23. Zhao J, Gao Z, Mei H, Li Y, Wang Y. Differentiation of human mesenchymal stem cells: the potential mechanism for estrogen-induced preferential osteoblast versus adipocyte differentiation. Am J Med Sci. 2011;341:460-8 pubmed publisher
    ..of hMSCs to osteoblasts in contrast to adipocytes, the former of which was mediated through the PI3K/SSH1L but not the mitogen-activated protein kinase pathway...
  24. Peterburs P, Heering J, Link G, Pfizenmaier K, Olayioye M, Hausser A. Protein kinase D regulates cell migration by direct phosphorylation of the cofilin phosphatase slingshot 1 like. Cancer Res. 2009;69:5634-8 pubmed publisher
    ..In this study, we provide evidence that the cofilin phosphatase slingshot 1 like (SSH1L), an important regulator of the complex actin remodeling machinery, is a novel in vivo PKD substrate...
  25. Huang T, Minamide L, Bamburg J, Bokoch G. Chronophin mediates an ATP-sensing mechanism for cofilin dephosphorylation and neuronal cofilin-actin rod formation. Dev Cell. 2008;15:691-703 pubmed publisher
  26. Zhou L, Jones E, Murai K. EphA signaling promotes actin-based dendritic spine remodeling through slingshot phosphatase. J Biol Chem. 2012;287:9346-59 pubmed publisher
    ..alters F-actin distribution in spines, and causes transient spine elongation through the phosphatases slingshot 1 (SSH1) and calcineurin/protein phosphatase 2B (PP2B)...
  27. Zhang W, Zhao H, Zhou F, Li W, Cai S. [Localization and expression of Slingshot-1L in peripheral eosinophils from patients with acute asthma exacerbation]. Nan Fang Yi Ke Da Xue Xue Bao. 2011;31:928-32 pubmed
    ..The efficacy of inhaled corticosteroids in asthma control might be partly attributed to a down-regulated expression of SSH-1L. ..
  28. Kim J, Huang T, Bokoch G. Reactive oxygen species regulate a slingshot-cofilin activation pathway. Mol Biol Cell. 2009;20:2650-60 pubmed publisher
    ..These results suggest that the formation of ROS by NADPH oxidases engages a SSH-1L-cofilin pathway to regulate cytoskeletal organization and cell migration. ..
  29. Kligys K, Yao J, Yu D, Jones J. 14-3-3zeta/tau heterodimers regulate Slingshot activity in migrating keratinocytes. Biochem Biophys Res Commun. 2009;383:450-4 pubmed publisher
    ..Here, we assayed the role of 14-3-3 isoforms in regulating the activity of SSH1. Using amino or carboxy terminal domains of 14-3-3zeta, we demonstrate that in keratinocytes 14-3-3zeta/tau ..
  30. Song S, Kang M, Yoo N, Lee S. Mutational analysis of mononucleotide repeats in dual specificity tyrosine phosphatase genes in gastric and colon carcinomas with microsatellite instability. APMIS. 2010;118:389-93 pubmed publisher
    ..By analyzing a public genomic database, we found that five DPTP genes, CDC14A, MTM1, MTMR3, SSH1, and SSH2, have mononucleotide repeats in their coding DNA sequences...
  31. Kligys K, Claiborne J, DeBiase P, Hopkinson S, Wu Y, Mizuno K, et al. The slingshot family of phosphatases mediates Rac1 regulation of cofilin phosphorylation, laminin-332 organization, and motility behavior of keratinocytes. J Biol Chem. 2007;282:32520-8 pubmed
    ..Keratinocytes express all members of the SSH family (SSH1, SSH2, and SSH3) and CIN...
  32. Eiseler T, Döppler H, Yan I, Kitatani K, Mizuno K, Storz P. Protein kinase D1 regulates cofilin-mediated F-actin reorganization and cell motility through slingshot. Nat Cell Biol. 2009;11:545-56 pubmed publisher
    ..Here we show that in response to RhoA activation, protein kinase D1 (PKD1) phosphorylates the SSH enzyme SSH1L at a serine residue located in its actin-binding motif...
  33. He P, Yip W, Chai B, Chai B, Jabar M, Dusa N, et al. Inhibition of cell migration and invasion by miR?29a?3p in a colorectal cancer cell line through suppression of CDC42BPA mRNA expression. Oncol Rep. 2017;38:3554-3566 pubmed publisher
    ..77-fold), in the array were upregulated by miR?29a?3p. A significant increase in expression IQGAP2, PHLDB2, SSH1 mRNAs and downregulation of PAK1 mRNA was also detected with miR?29a?3p inhibition...
  34. Homma Y, Kanno S, Sasaki K, Nishita M, Yasui A, Asano T, et al. Insulin receptor substrate-4 binds to Slingshot-1 phosphatase and promotes cofilin dephosphorylation. J Biol Chem. 2014;289:26302-13 pubmed publisher
    ..Slingshot-1 (SSH1) is a protein phosphatase that plays a crucial role in regulating actin dynamics by dephosphorylating and ..
  35. Zheng K, Xiang Y, Wang Q, Jin F, Chen M, Ma K, et al. Calcium-signal facilitates herpes simplex virus type 1 nuclear transport through slingshot 1 and calpain-1 activation. Virus Res. 2014;188:32-7 pubmed publisher
    ..Besides, calpain-1, a calcium-dependent cysteine protease, was involved in viral intracellular migration. These results may lead to new targets for antiviral therapy. ..
  36. Zhou Y, Liu J, Fu X, Yu Y, Shi B, Yu G, et al. Identification of three novel frameshift mutations of the MVK gene in four Chinese families with disseminated superficial actinic porokeratosis. Br J Dermatol. 2013;169:193-5 pubmed publisher
  37. Li X, Zhou Q, Zhu L, Zhao Z, Wang P, Zhang L, et al. [Analysis of clinical and genetic features of nine patients with disseminated superfacial actinic porokeratosis]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2017;34:481-485 pubmed publisher
    ..potential mutations of four genes (MVK, MVD, PMVK, FDPS) involved in the mevalonate pathway as well as SLC17A9, SSH1, and SART3 genes. Pathogenecity of suspected mutations were assessed with SIFT, and Polyphen-2 scores. A c...
  38. Dai S, Sarmiere P, Wiggan O, Bamburg J, Zhou D. Efficient Salmonella entry requires activity cycles of host ADF and cofilin. Cell Microbiol. 2004;6:459-71 pubmed
    ..We propose that ADF and cofilin actin-dynamizing activities and their activity cycling via phosphorylation are required for efficient Salmonella internalization. ..
  39. Takahashi K, Okabe H, Kanno S, Nagai T, Mizuno K. A pleckstrin homology-like domain is critical for F-actin binding and cofilin-phosphatase activity of Slingshot-1. Biochem Biophys Res Commun. 2017;482:686-692 pubmed publisher
    Slingshot-1 (SSH1) is a protein phosphatase that specifically dephosphorylates and activates cofilin, an F-actin-severing protein...
  40. Zhao J, Zhang M, Ji Q, Xing F, Meng L, Wang Y. The role of slingshot-1L (SSH1L) in the differentiation of human bone marrow mesenchymal stem cells into cardiomyocyte-like cells. Molecules. 2012;17:14975-94 pubmed publisher
    ..In this study, we found that SSH1L promoted morphology changes of microfilaments during differentiation but was inhibited by the inhibitors of actin ..
  41. Takahashi K, Kanno S, Mizuno K. Activation of cytosolic Slingshot-1 phosphatase by gelsolin-generated soluble actin filaments. Biochem Biophys Res Commun. 2014;454:471-7 pubmed publisher
    Slingshot-1 (SSH1) is a protein phosphatase that dephosphorylates and activates cofilin, an actin-severing and -disassembling protein. SSH1 is bound to and activated by F-actin, but not G-actin...
  42. Leonard A, Marando C, Rahman A, Fazal F. Thrombin selectively engages LIM kinase 1 and slingshot-1L phosphatase to regulate NF-?B activation and endothelial cell inflammation. Am J Physiol Lung Cell Mol Physiol. 2013;305:L651-64 pubmed publisher
    ..Thus this study provides evidence for a novel role of LIMK1 and SSH-1L in selectively regulating EC inflammation associated with intravascular coagulation. ..
  43. Barisic S, Nagel A, Franz Wachtel M, Macek B, Preiss A, Link G, et al. Phosphorylation of Ser 402 impedes phosphatase activity of slingshot 1. EMBO Rep. 2011;12:527-33 pubmed publisher
    ..we have identified Ser 402 as a new phosphorylation site within the catalytic domain of human slingshot 1 (SSH1)...
  44. Zhang Z, Niu Z, Yuan W, Liu W, Xiang L, Zhang J, et al. Fine mapping and identification of a candidate gene SSH1 in disseminated superficial actinic porokeratosis. Hum Mutat. 2004;24:438 pubmed
    ..Upon screening 30 candidate genes, we identified a missense mutation, p.Ser63Asn in SSH1 in one family, a frameshift mutation, p...
  45. Kurita S, Watanabe Y, Gunji E, Ohashi K, Mizuno K. Molecular dissection of the mechanisms of substrate recognition and F-actin-mediated activation of cofilin-phosphatase Slingshot-1. J Biol Chem. 2008;283:32542-52 pubmed publisher
    Slingshot-1 (SSH1), a member of a dual-specificity protein phosphatase family, regulates actin dynamics by dephosphorylating and reactivating cofilin, an actin-depolymerizing factor...
  46. San Martin A, Lee M, Williams H, Mizuno K, LASSEGUE B, Griendling K. Dual regulation of cofilin activity by LIM kinase and Slingshot-1L phosphatase controls platelet-derived growth factor-induced migration of human aortic smooth muscle cells. Circ Res. 2008;102:432-8 pubmed
    ..We found that VSMCs express SSH1L, which is induced and activated (564+/-73 versus 1021+/-141 picomoles of PO(4); P=0.015) by PDGF...