PIPKI-PIP2 promotes cell migration by recruiting Smurf1 to the membrane and increasing its activity.

Smurf1 is a member of the Nedd4 family of E3 ubiquitin ligases. Numerous lines of evidence indicate that the membrane localization of Smurf1 is essential for its activity. However, the underlying mechanisms that regulate the membrane localization of Smurf1 remain unclear. Type I phosphatidylinositol phosphate kinase (PIPKI) is a phosphatidylinositol kinase that generates phosphatidylinositol 4,5-bisphosphate (PIP2), which is located in the plasma membrane and regulates cellular processes, including ion channel activity and cell migration. In this study, we show that PIP2 and PIPKI regulate the membrane translocation of Smurf1. Importantly, the recruitment of Smurf1 to the cell membrane through the association of its C2 domain with PIPKI-produced PIP2 is essential for Smurf1-mediated E3 ligase activity and cell migration. Therefore, we identify a PIPKI-PIP2-Smurf1 signaling axis that regulates cell migration.

• Publication year

  2025

• Venue

  Acta Biochimica et Biophysica Sinica

• Publication date

  2025-11-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.3724/abbs.2025217PMID 41466454
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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