Evidence for a conserved role for CRKII and Rac in engulfment of apoptotic cells.

Tosello-Trampont, A C; Brugnera, E; Ravichandran, K S

Tosello-Trampont, A C; Brugnera, E; Ravichandran, K S.

Afiliación

Tosello-Trampont AC; Beirne B. Carter Center for Immunology Research and the Department of Microbiology, University of Virginia, Charlottesville 22908, USA.

J Biol Chem ; 276(17): 13797-802, 2001 Apr 27.

Article en En | MEDLINE | ID: mdl-11297528

RESUMEN

Apoptosis or programmed cell death occurs in multicellular organisms throughout life. The removal of apoptotic cells by phagocytes prevents secondary necrosis and inflammation and also plays a key role in tissue remodeling and regulating immune responses. The molecular mechanisms that regulate the engulfment of apoptotic cells are just beginning to be elucidated. Recent genetic studies in the nematode Caenorhabditis elegans have implicated at least six genes in the removal of apoptotic cell corpses. The gene products of ced-2, ced-5, and ced-10 are thought to be part of a pathway that regulates the reorganization of the cytoskeleton during engulfment. The adapter proteins CrkII and Dock180 and the small GTPase Rac represent the mammalian orthologues of the ced-2, ced-5 and ced-10 gene products, respectively. It is not known whether CrkII, Dock180, or Rac proteins have any role during engulfment in mammalian cells. Here we show, using stable cell lines and transient transfections, that overexpression of wild-type CrkII or an activated form of Rac1 enhances engulfment. Mutants of CrkII failed to mediate this increased engulfment. The higher CrkII-mediated uptake was inhibited by coexpression of a dominant negative form of Rac1 but not by a dominant a negative Rho protein; this suggested that Rac functions downstream of CrkII in this process, which is consistent with genetic studies in the worm that place ced-10 (rac) downstream of ced-2 (crk) in cell corpse removal. Taken together, these data suggest that CED-2/CrkII and CED-10/Rac are part of an evolutionarily conserved pathway in engulfment of apoptotic cells.

Asunto(s)

Apoptosis; Proteínas Quinasas/química; Proteínas Proto-Oncogénicas; Proteínas de Unión al GTP rac/fisiología; Animales; Línea Celular; Secuencia Conservada; Cricetinae; Relación Dosis-Respuesta a Droga; Citometría de Flujo; Genes Dominantes; Modelos Biológicos; Fagocitosis; Plásmidos/metabolismo; Estructura Terciaria de Proteína; Proteínas Proto-Oncogénicas c-crk; Transducción de Señal; Transfección; Proteínas de Unión al GTP rac/química; Proteínas de Unión al GTP rac/metabolismo; Proteína de Unión al GTP rac1/genética; Proteína de Unión al GTP rac1/metabolismo; Proteínas de Unión al GTP rho/genética; Proteínas de Unión al GTP rho/metabolismo; Dominios Homologos src

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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Quinasas / Proteínas Proto-Oncogénicas / Apoptosis / Proteínas de Unión al GTP rac Límite: Animals Idioma: En Revista: J Biol Chem Año: 2001 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

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