title: Adaptor protein cerebral cavernous malformation 3 (CCM3) mediates phosphorylation of the cytoskeletal proteins ezrin/radixin/moesin by mammalian Ste20-4 to protect cells from oxidative stress.
abstract: While studying the functions of CCM3/PDCD10, a gene encoding an adaptor protein whose mutation results in vascular malformations, we have found that it is involved in a novel response to oxidative stress that results in phosphorylation and activation of the ezrin/radixin/moesin (ERM) family of proteins. This phosphorylation protects cells from accidental cell death induced by oxidative stress. We also present evidence that ERM phosphorylation is performed by the GCKIII kinase Mst4, which is activated and relocated to the cell periphery after oxidative stress. The cellular levels of Mst4 and its activation after oxidative stress depend on the presence of CCM3, as absence of the latter impairs the phosphorylation of ERM proteins and enhances death of cells exposed to reactive oxygen species. These findings shed new light on the response of cells to oxidative stress and identify an important pathophysiological situation in which ERM proteins and their phosphorylation play a significant role.
authors.affiliation: Department of Physiology and Centro Singular de Medicina Molecular y Enfermedades Crónicas (CIMUS), University of Santiago de Compostela, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Fidalgo
authors.forename: Ana
authors.initials: A
authors.lastname: Guerrero
authors.forename: María
authors.initials: M
authors.lastname: Fraile
authors.forename: Cristina
authors.initials: C
authors.lastname: Iglesias
authors.forename: Celia M
authors.initials: CM
authors.lastname: Pombo
authors.forename: Juan
authors.initials: J
authors.lastname: Zalvide
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D016923:Cell Death; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism; D018384:Oxidative Stress; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D000099149:Ezrin; D000099317:Hippo Kinases
chemical_list: D051017:Apoptosis Regulatory Proteins; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000099149:Ezrin; C495390:PDCD10 protein, human; C071058:moesin; C071776:radixin; C430908:STK26 protein, human; D000099317:Hippo Kinases