Work

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

Year: 2025

Type: article

Abstract: 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.

Source: Acta Biochimica et Biophysica Sinica

DOI: 10.3724/abbs.2025217

Authors: Yuxin Chen, Xiao Tan, Meiling Lu, Yunfei Chen, Weijuan Pan, Rong Wei, Yingcong Wang

Institutions: Tongji University, China Pharmaceutical University, Shanghai Tenth People's Hospital, East China Normal University

Language: English

Topic: Protein Kinase Regulation and GTPase Signaling

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: diamond

OpenAlex ID: W4416131585

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Cites: 28

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