Differential activities, subcellular distribution and tissue expression patterns of three members of Slingshot family phosphatases that dephosphorylate cofilin

Yusaku Ohta, Kazuyoshi Kousaka, Kyoko Nagata-Ohashi, Kazumasa Ohashi, Aya Muramoto, Yasuyuki Shima, Ryusuke Niwa, Tadashi Uemura, Kensaku Mizuno

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91 Citations (Scopus)

Abstract

Background: Cofilin, a key regulator of actin filament dynamics, is inactivated by phosphorylation at Ser-3 by LIM-kinases and is reactivated by dephosphorylation by a family of protein phosphatases, termed Slingshot (SSH). Results: We have identified two novel isoforms of SSHs, termed SSH-2L and SSH-3L and characterized them in comparison with SSH-1L that was previously reported. SSH-1L and SSH-2L, but not SSH-3L, tightly bound to and co-localized with actin filaments. When expressed in cultured cells, SSH-1L, SSH-2L and SSH-3L decreased the level of Ser-3-phosphorylated cofilin (P-cofilin) in cells and suppressed LIM-kinase-induced actin reorganization, although SSH-3L was less effective than SSH-1L and SSH-2L. In cell-free assays, SSH-1L and SSH-2L efficiently dephosphorylated P-cofilin, whereas SSH-3L did do so only weakly. Using deleted mutants of SSH-1L and SSH-2L, we found that the N-terminal and C-terminal extracatalytic regions are critical for cofilin-phosphatase and F-actin-binding activities, respectively. In situ hybridization analyses revealed characteristic patterns of expression of each of the mouse Ssh genes in both neuronal and non-neuronal tissues; in particular, expression of Ssh-3 in epithelial tissues is evident. Conclusion: SSH-1L, SSH-2L and SSH-3L have the potential to dephosphorylate P-cofilin, but subcellular distribution, F-actin-binding activity, specific phosphatase activity and expression patterns significantly differ, which suggests that they have related but distinct functions in various cellular and developmental event.

Original languageEnglish
Pages (from-to)811-824
Number of pages14
JournalGenes to Cells
Volume8
Issue number10
DOIs
Publication statusPublished - 2003 Oct

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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