Glycodelin-A protein interacts with Siglec-6 protein to suppress trophoblast invasiveness by down-regulating extracellular signal-regulated kinase (ERK)/c-Jun signaling pathway.

Lam, Kevin K W; Chiu, Philip C N; Lee, Cheuk-Lun; Pang, Ronald T K; Leung, Carmen O N; Koistinen, Hannu; Seppala, Markku; Ho, Pak-Chung; Yeung, William S B

Lam, Kevin K W; Chiu, Philip C N; Lee, Cheuk-Lun; Pang, Ronald T K; Leung, Carmen O N; Koistinen, Hannu; Seppala, Markku; Ho, Pak-Chung; Yeung, William S B.

Afiliación

Lam KK; Department of Obstetrics and Gynaecology, The University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong, China.

J Biol Chem ; 286(43): 37118-27, 2011 Oct 28.

Article en En | MEDLINE | ID: mdl-21880722

RESUMEN

During placentation, the cytotrophoblast differentiates into the villous cytotrophoblast and the extravillous cytotrophoblast. The latter invades the decidualized endometrium. Glycodelin-A (GdA) is abundantly synthesized by the decidua but not the trophoblast. Previous data indicate that GdA suppresses the invasion of trophoblast cell lines by down-regulating proteinase expression and activities. This study addresses the signaling pathway involved in the above phenomenon. GdA was found to suppress phosphorylation of ERKs and expression of their downstream effector c-Jun, a component of the transcription factor activator protein-1 (AP-1). The involvement of ERKs and c-Jun in suppressing trophoblast invasion and biosynthesis of proteinases was confirmed by using siRNA knockdown and pharmacological inhibitors. Desialylation reduced binding affinity of GdA toward and invasion suppressive activities on the trophoblast. Co-immunoprecipitation showed that Siglec-6 on the trophoblast was the binding protein of GdA. The binding of GdA to Siglec-6 was sialic acid-dependent. Treatment with anti-Siglec-6 antibody abolished the invasion suppressive activities of GdA. These results show that GdA interacts with Siglec-6 to suppress trophoblast invasiveness by down-regulating the ERK/c-Jun signaling pathway.

Asunto(s)

Antígenos CD/metabolismo; Antígenos de Diferenciación Mielomonocítica/metabolismo; Endometrio/metabolismo; Quinasas MAP Reguladas por Señal Extracelular/metabolismo; Glicoproteínas/metabolismo; Lectinas/metabolismo; Sistema de Señalización de MAP Quinasas/fisiología; Proteínas Gestacionales/metabolismo; Proteínas Proto-Oncogénicas c-jun/metabolismo; Trofoblastos/metabolismo; Antígenos CD/genética; Antígenos de Diferenciación Mielomonocítica/genética; Línea Celular; Endometrio/citología; Quinasas MAP Reguladas por Señal Extracelular/genética; Femenino; Glicodelina; Glicoproteínas/genética; Humanos; Lectinas/genética; Proteínas Gestacionales/genética; Unión Proteica; Proteínas Proto-Oncogénicas c-jun/genética; Factor de Transcripción AP-1/genética; Factor de Transcripción AP-1/metabolismo; Trofoblastos/citología

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Gestacionales / Trofoblastos / Glicoproteínas / Antígenos de Diferenciación Mielomonocítica / Antígenos CD / Proteínas Proto-Oncogénicas c-jun / Sistema de Señalización de MAP Quinasas / Quinasas MAP Reguladas por Señal Extracelular / Endometrio / Lectinas Límite: Female / Humans Idioma: En Revista: J Biol Chem Año: 2011 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos

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