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Disordered Region in PI3K Regulatory Subunit p85 Drives Clathrin‐dependent Endocytosis and Regulates Cell Motility
Author(s) -
Matsubayashi Hideaki,
Mountain Jack,
Peterson Amy,
Inoue Takanari
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.01941
Subject(s) - endocytosis , clathrin , microbiology and biotechnology , receptor mediated endocytosis , protein subunit , signal transducing adaptor protein , chemistry , biology , cell , signal transduction , biochemistry , gene
Class 1A PI3Ks are lipid kinases composed of catalytic subunit p110 and regulatory subunit p85. Besides its catalytic activity of PI(3,4,5)P3 production, PI3K has been implicated in the process of receptor endocytosis. However, it remained unclear if and how directly class 1A PI3K engages endocytosis machinery. We found that a disordered region in the inter‐SH2 (iSH2) domain of regulatory subunit p85 has binding motifs for AP‐2, an adaptor protein complex for clathrin, and its plasma membrane targeting drives clathrin‐mediated endocytosis. Remarkably, this endocytosis induction is independent of lipid kinase activity. Mutation of the endocytosis motifs in p85 caused its focal adhesion accumulation and increased random migration of mouse embryonic fibroblasts (MEFs). This newly discovered aspect of p85 would be a central piece to comprehensively understand the regulation of PI3K and its effect on cell dynamics.