RhoB regulates PDGFR-beta trafficking and signaling in vascular smooth muscle cells.
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-beta (PDGFR-beta) in vascular smooth muscle cells.


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-beta 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-beta 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.


CONCLUSIONS
Our findings establish RhoB as a critical regulator of PDGFR-beta trafficking and signaling in vascular smooth muscle cells.
Huang
Minzhou
M
Lankenau Institute for Medical Research, 100 E. Lancaster Avenue, Wynnewood PA 19096. Laury-Kleintop@limr.org.
Duhadaway
James B
JB
Prendergast
George C
GC
Laury-Kleintop
Lisa D
LD
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D011992:Endosomes / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000201:enzymology / Q000378:metabolism*; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D021381:Protein Transport; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism*; D015398:Signal Transduction; D022161:Transport Vesicles / Q000378:metabolism; D020743:rhoB GTP-Binding Protein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism
D010982:Platelet-Derived Growth Factor; D020797:Receptor, Platelet-Derived Growth Factor beta; D019061:src-Family Kinases; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020743:rhoB GTP-Binding Protein