The present invention provides a method for modulating the activity of Rac1, comprising modifying the phosphorylation state of Ser179 in syndecan-4 through influencing the interaction between syndecan-4 and the guanin nucleotide exchange factor of Rac1 (RacGEF) named Tiam1 in a GTP-dependent manner. In particular, methods are provided for enhancing the epithelial phenotype of a cell and for initiating the polarization of a cell by increasing the de-phosphorylation of said Ser179 of syndecan-4, and for enhancing the migratory phenotype of a cell and for initiating the neuronal differentiation of a cell by increasing the phosphorylation of said Ser179 of syndecan-4. Polypeptides for use in modulating the activity of the small GTPase Rac are also provided, as well as a method for identifying an agent capable of indirectly modulating the activity of the small GTPase Rac 1.
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