A pleckstrin homology-like domain is critical for F-actin binding and cofilin-phosphatase activity of Slingshot-1.

Slingshot-1 (SSH1) is a protein phosphatase that specifically dephosphorylates and activates cofilin, an F-actin-severing protein. SSH1 binds to and co-localizes with F-actin, and the cofilin-phosphatase activity of SSH1 is markedly increased by binding to F-actin. In this study, we performed a secondary structure analysis of SSH1, which predicted the existence of a pleckstrin homology (PH)-like domain in the N-terminal region of SSH1. SSH1 also contains a DEK-C domain in the N-terminal region. The N-terminal fragment of SSH1 bound to and co-localized with F-actin, but mutation at Arg-96 or a Leu-His-Lys (LHK) motif in the PH-like domain reduced this activity. Furthermore, mutation at Arg-96 abrogated the cofilin-phosphatase activity of SSH1 in the presence of F-actin. These results suggest that the N-terminal PH-like domain plays a critical role in F-actin binding and F-actin-mediated activation of the cofilin-phosphatase activity of SSH1.

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