The RhoA-Rok-myosin II pathway is involved in extracellular matrix-mediated regulation of prolactin signaling in mammary epithelial cells.
Bottom Line: Under these culture conditions, the RhoA pathway is activated, leading to downregulation of prolactin receptor expression and reduced prolactin signaling.In addition, inhibition of myosin II ATPase activity by blebbistatin also exerts a beneficial effect on prolactin receptor expression and prolactin signaling, suggesting that tension exerted by the collagen substratum, in collaboration with the RhoA-Rok-myosin II pathway, contributes to the failure of prolactin signaling.They display high levels of RhoA activity and are inefficient in prolactin signaling, stressing the importance of matrix stiffness in signal transduction.
Affiliation: Institute of Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan, ROC.Show MeSH
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Mentions: The mutual antagonism between Rac and Rho GTPases has been well documented (Nimnual et al., 2003; Ohta et al., 2006; Takefuji et al., 2007; Bustos et al., 2008). Given that Rac1 is essential for optimal prolactin signaling in MECs, we asked if the effect of RhoA pathway on prolactin signaling was mediated by inhibiting Rac1 (Akhtar and Streuli, 2006). Rac activity was therefore assessed in response to alterations of RhoA and Rok activity. Inhibition of Rok by Y27632 resulted in elevated Rac activity in cells cultured on collagen I, while constitutively active L63RhoA reduced Rac activity in cells cultured on BM (Fig. 7).
Affiliation: Institute of Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan, ROC.