Non-catalytic role of phosphoinositide 3-kinase in mesenchymal cell migration through non-canonical induction of p85β/AP-2-mediated endocytosis.

ABSTRACT: Class IA phosphoinositide 3-kinase (PI3K) galvanizes fundamental cellular processes such as migration, proliferation, and differentiation. To enable multifaceted roles, the catalytic subunit p110 utilizes a multi-domain, regulatory subunit p85 through its inter SH2 domain (iSH2). In cell migration, their product PI(3,4,5)P ₃ generates locomotive activity. While non-catalytic roles are also implicated, underlying mechanisms and its relationship to PI(3,4,5)P ₃ signaling remain elusive. Here, we report that a disordered region of iSH2 contains previously uncharacterized AP-2 binding motifs which can trigger clathrin and dynamin-mediated endocytosis independent of PI3K catalytic activity. The AP-2 binding motif mutants of p85 aberrantly accumulate at focal adhesions and

SUBMITTER: Matsubayashi H 

PROVIDER: S-EPMC9882665 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature