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Phosphorylation of serine 106 in Asef2 regulates cell migration and adhesion turnover.
Evans, J Corey; Hines, Kelly M; Forsythe, Jay G; Erdogan, Begum; Shi, Mingjian; Hill, Salisha; Rose, Kristie L; McLean, John A; Webb, Donna J.
Afiliación
  • Evans JC; Department of Biological Sciences and Vanderbilt Kennedy Center for Research on Human Development, ‡Department of Chemistry, §Vanderbilt Institute for Chemical Biology (VICB), ∥Vanderbilt Institute for Integrative Biosystems Research and Education (VIIBRE), ⊥Mass Spectrometry Research Center, #Department of Biochemistry, and ●Department of Cancer Biology, Vanderbilt University , Nashville, Tennessee 37235, United States.
J Proteome Res ; 13(7): 3303-13, 2014 Jul 03.
Article en En | MEDLINE | ID: mdl-24874604
Asef2, a 652-amino acid protein, is a guanine nucleotide exchange factor (GEF) that regulates cell migration and other processes via activation of Rho family GTPases, including Rac. Binding of the tumor suppressor adenomatous polyposis coli (APC) to Asef2 is known to induce its GEF activity; however, little is currently known about other modes of Asef2 regulation. Here, we investigated the role of phosphorylation in regulating Asef2 activity and function. Using high-resolution mass spectrometry (MS) and tandem mass spectrometry (MS/MS), we obtained complete coverage of all phosphorylatable residues and identified six phosphorylation sites. One of these, serine 106 (S106), was particularly intriguing as a potential regulator of Asef2 activity because of its location within the APC-binding domain. Interestingly, mutation of this serine to alanine (S106A), a non-phosphorylatable analogue, greatly diminished the ability of Asef2 to activate Rac, while a phosphomimetic mutation (serine to aspartic acid, S106D) enhanced Rac activation. Furthermore, expression of these mutants in HT1080 cells demonstrated that phosphorylation of S106 is critical for Asef2-promoted migration and for cell-matrix adhesion assembly and disassembly (adhesion turnover), which is a process that facilitates efficient migration. Collectively, our results show that phosphorylation of S106 modulates Asef2 GEF activity and Asef2-mediated cell migration and adhesion turnover.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Adhesión Celular / Movimiento Celular / Procesamiento Proteico-Postraduccional / Factores de Intercambio de Guanina Nucleótido Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: J Proteome Res Asunto de la revista: BIOQUIMICA Año: 2014 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Adhesión Celular / Movimiento Celular / Procesamiento Proteico-Postraduccional / Factores de Intercambio de Guanina Nucleótido Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: J Proteome Res Asunto de la revista: BIOQUIMICA Año: 2014 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos