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: Rok is a key effector of RhoA, and we therefore tested its involvement in the inhibition of prolactin signaling in MECs cultured on collagen I. For these experiments, we either added the Rok inhibitor, Y27632 to cultures, or expressed dominant negative Rok (RB/PH (TT)). In both cases, blocking the action of Rok enhanced prolactin receptor expression (Fig. 5A), as well as prolactin-induced Stat5 phosphorylation (Fig. 5B) and β-casein expression (Fig. 5A,C).
Affiliation: Institute of Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan, ROC.