title: Slingshot-3 dephosphorylates ADF/cofilin but is dispensable for mouse development.
abstract: Actin-depolymerizing factor (ADF) and cofilin constitute a family of key regulators of actin filament dynamics. ADF/cofilin is inactivated by phosphorylation at Ser-3 by LIM-kinases and reactivated by dephosphorylation by Slingshot (SSH) family phosphatases. Defects in LIM kinases or ADF/cofilin have been implicated in morbidity in human or mice; however, the roles of mammalian SSH in vivo have not been addressed. In this study, we examined the endogenous expression of each mouse SSH member in various cell lines and tissues, and showed that SSH-3L protein was strongly expressed in epithelial cells. Our structure-function analysis of SSH-3L suggested the possibility that the C-tail unique to SSH-3L negatively regulates the catalytic activity of this phosphatase. Furthermore we made ssh-3 knockout mice to examine its potential in vivo roles. Unexpectedly, ssh-3 was not essential for viability, fertility, or development of epithelial tissues; and ssh-3 did not genetically modify the corneal disorder of the corn1/ADF/destrin mutant.
authors.affiliation: Graduate of School of Science, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Kousaka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyonari
authors.forename: Naoko
authors.initials: N
authors.lastname: Oshima
authors.forename: Akira
authors.initials: A
authors.lastname: Nagafuchi
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Shima
authors.forename: Osamu
authors.initials: O
authors.lastname: Chisaka
authors.forename: Tadashi
authors.initials: T
authors.lastname: Uemura
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000201:enzymology; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D051338:Cofilin 1 / Q000378:metabolism*; D004848:Epithelium / Q000196:embryology / Q000201:enzymology; D005298:Fertility / Q000235:genetics; D005328:Fetal Viability / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D041681:NIH 3T3 Cells; D010749:Phosphoprotein Phosphatases / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D017386:Sequence Homology, Amino Acid
chemical_list: D051338:Cofilin 1; D010749:Phosphoprotein Phosphatases; C529575:SSH1 protein, mouse; C529574:SSH3 protein, mouse