RhoB Links PDGF Signaling to Cell Migration by Coordinating Activation and Localization of Cdc42 and Rac

Lankenau Institute for Medical Research, Wynnewood, Pennsylvania 19096, USA.
Journal of Cellular Biochemistry (Impact Factor: 3.26). 06/2011; 112(6):1572-84. DOI: 10.1002/jcb.23069
Source: PubMed


The small GTPase RhoB regulates endocytic trafficking of receptor tyrosine kinases (RTKs) and the non-receptor kinases Src and Akt. While receptor-mediated endocytosis is critical for signaling processes driving cell migration, mechanisms that coordinate endocytosis with the propagation of migratory signals remain relatively poorly understood. In this study, we show that RhoB is essential for activation and trafficking of the key migratory effectors Cdc42 and Rac in mediating the ability of platelet-derived growth factor (PDGF) to stimulate cell movement. Stimulation of the PDGF receptor-β on primary vascular smooth muscle cells (VSMCs) results in RhoB-dependent trafficking of endosome-bound Cdc42 from the perinuclear region to the cell periphery, where the RhoGEF Vav2 and Rac are also recruited to drive formation of circular dorsal and peripheral ruffles necessary for cell migration. Our findings identify a novel RhoB-dependent endosomal trafficking pathway that integrates RTK endocytosis with Cdc42/Rac localization and cell movement.

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Available from: George C Prendergast
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    • "While RhoA, Rac and Cdc42 localize to the plasma membrane and are involved in receptor internalization, RhoB is found both at the plasma membrane and endosomes and has been suggested to regulate endosomal traffic [14]. RhoB is involved in traffic to the cell surface, nucleus, or lysosome, and/or activation of a number of signaling molecules, such as RTKs, Akt and Src [15], [16], [17]. It has recently been reported that activated RhoB promotes the polymerization of an actin coat around endosomes and association of these vesicles to subcortical actin cables, thus effectively inhibiting further endosomal transport [18]. "
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    • "RhoB has been shown to play a role in growth factor receptor trafficking and through this mechanism can regulate growth factor receptor signaling under certain circumstances [9,10]. With this in mind, we became interested in determining whether RhoB regulated VEGF-induced angiogenic processes in endothelial cells, in order to identify possible novel targets which might ultimately be useful for enhancing the efficacy of current anti-VEGF/VEGFR blocking strategies. "
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