RRC ID 73125
Author Nakagawa K, Nagano T, Katasho R, Iwasaki T, Kamada S.
Title Integrin β1 transduces the signal for LY6D-induced macropinocytosis and mediates senescence-inducing stress-evoked vacuole formation via FAK.
Journal FEBS Lett
Abstract Cellular senescence is a highly stable cell-cycle arrest induced by DNA damage and various cellular stresses. Recently, we have revealed that lymphocyte antigen 6 complex, locus D (LY6D) is responsible for senescence-inducing stress-evoked vacuole formation through induction of Src family kinase (SFK)-mediated macropinocytosis. However, the signaling molecule(s) transducing the macropinocytosis signal from extracellular LY6D to the cytoplasmic SFK are unknown. In this study, we identified integrin β1, a transmembrane signaling protein, as an interactor of LY6D by proteomic analysis and co-immunoprecipitation assays. Inhibition of integrin β1 impaired LY6D-induced macropinocytosis, and integrin β1 activated SFK through focal adhesion kinase to mediate macropinocytosis. These results indicate that integrin β1 is a crucial mediator of the LY6D-induced vacuole formation in senescent cells.
Volume 596(21)
Pages 2768-2780
Published 2022-11-1
DOI 10.1002/1873-3468.14477
PMID 35999651
MeSH Focal Adhesion Kinase 1 / genetics Focal Adhesion Kinase 1 / metabolism Focal Adhesion Protein-Tyrosine Kinases / metabolism Integrin beta1* / genetics Integrin beta1* / metabolism Phosphorylation Proteomics* Signal Transduction / physiology Vacuoles / metabolism src-Family Kinases / metabolism
IF 3.057
DNA material Genome Network Project Human cDNA Clone IRAK026E17 (HGX010513)