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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:2597.)
© 2007 American Heart Association, Inc.

Vascular Biology

RhoB Regulates PDGFR-β Trafficking and Signaling in Vascular Smooth Muscle Cells

Minzhou Huang; James B. DuHadaway; George C. Prendergast; Lisa D. Laury-Kleintop

From the Lankenau Institute for Medical Research (M.H., J.B.D., G.C.P., L.D.L.-K.), Wynnewood Pa; and the Department of Pathology, Anatomy, and Cell Biology and Kimmel Cancer Center (G.C.P.), Thomas Jefferson University, Philadelphia Pa.

Correspondence to Lisa D. Laury-Kleintop, Lankenau Institute for Medical Research, 100 E. Lancaster Avenue, Wynnewood PA 19096. E-mail Laury-Kleintop{at}limr.org

Objective— RhoB is a small GTPase localized at the plasma membrane and endosomes that participates in the regulation of endocytic trafficking of the epidermal growth factor (EGF) receptor and the nonreceptor kinases Src and Akt. This study was performed to determine whether RhoB plays a critical role in trafficking and signaling by the platelet-derived growth factor receptor-β (PDGFR-β) in vascular smooth muscle cells.

Methods and Results— Cells derived from RhoB knockout mice failed to proliferate in response to PDGF, and downstream signaling was compromised as reflected by reduced phosphorylation of the effector kinases Akt and ERK1/2. In normal cells, PDGF stimulated trafficking of PDGFR-β into a perinuclear late endosomal compartment and triggered entry of Src, Akt, extracellular signal-regulated kinase (ERK) into the cell nucleus. In contrast, PDGF treatment of RhoB null cells resulted in neither PDGFR-β trafficking to late endosomes nor nuclear localization of Src, Akt, or ERK. In support of an essential function in these processes, restoring expression of RhoB in null cells rescued these defects and restored cell proliferation in response to PDGF.

Conclusion— Our findings establish RhoB as a critical regulator of PDGFR-β trafficking and signaling in vascular smooth muscle cells.

Herein, we show that in vascular smooth muscle cells RhoB plays a critical role in trafficking and signaling by the platelet-derived growth factor receptor-β. Cells derived from RhoB knockout mice failed to proliferate in response to PDGF and downstream signaling was compromised as reflected by reduced Akt and ERK1/2 phosphorylation.

Key Words: RhoB • platelet-derived growth factor receptor • endocytic trafficking • vascular smooth muscle cells

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