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C3G regulates megakaryocytic differentiation

AuthorsOrtiz-Rivero, Sara; Gutiérrez-Herrero, Sara; Martín-Granado, Víctor; Sequera, Celia; Porras, Almudena; Guerrero Arroyo, María del Carmen
Issue Date2015
CitationXXXXVIII Congreso de la Sociedad Española de Bioquímica y Biología Molecular (2015)
AbstractC3G (Crk-SH3-binding Guanine nucleotide Exchange Factor) is an activator of Ras family member Rap1/2. Several studies suggest a role for C3G in cell differentiation; C3G is induced during neural differentiation, as well as during differentiation of monocytic cells to macrophages. Similarly, enhancement in C3G protein and its association with Crk is required for adipocyte differentiation. Some evidences suggest a participation of C3G in the differentiation of megakaryocytes to platelets through Rap1 activation, although its potential role in early stages of megakaryocytic differentiation has not been addressed yet. Using erythroleukemic cell lines K562 and HEL we have found that C3G plays a role in the differentiation of immature cells to megakaryocytes, as overexpression of C3G increases the expression of megakaryocytic markers CD41 and CD61, while decreases erythroid marker glycophorin A. In contrast, the expression of CD41/CD61 decreases in C3G silenced cells. Morphology and polyploidisation analysis support the hypothesis of a positive role of C3G in megakaryocytic differentiation. This effect of C3G in megakaryopoiesis is dependent on PKC pathway as bisyndolylmaleimide completely abrogated it. Additionally, studies in double C3G/p38aMAPK K562 knockdown clones suggest a relationship between these two proteins in the regulation of K562 megakaryocytic differentiation. In concordance with the studies in cell lines, TPOstimulated bone marrow cells from megakaryocyte- and platelet-specific C3G transgenic mice showed higher levels of CD41/CD61 as compared to wild type cells. In contrast, bone marrow cells from C3GDCat transgenic mice showed lower levels of these megakaryocytic markers, indicating that the effect of C3G in megakaryocytic differentiation is Rap1-dependent.
DescriptionResumen del trabajo presentado al XXXXVIII Congreso de la Sociedad Española de Bioquímica y Biología Molecular (SEBBM), celebrado en Valencia del 7 al 10 de septiembre de 2015.
Appears in Collections:(IBMCC) Comunicaciones congresos
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