positive control for 16 and 26 hr. In wt cells, both addi-
tions induced the phosphorylation of Rb, whereas in
mutant cells the PDGF-AA-mediated response was
blocked (Figure 4G). We also followed phosphorylation
of cdc2 on tyrosine 15, which distinguishes G
entrance . In Tg737 cells only PDGF-BB, but not
PDGF-AA, increased cdc2 phosphorylation (Figure 4H),
whereas wt cells responded to both ligands, showing
that signaling through the cilium plays a major role in
PDGF-AA cell cycle regulation.
Our study shows that primary cilium formation corre-
lates with an elevation in PDGFRα expression and that
PDGFRα localizes with the cilium. It seems likely that
in quiescent fibroblasts PDGFRα-mediated signaling is
dependent upon its ciliary localization and that much of
the physiologically important PDGFRα signaling occurs
via the cilium. PDGFRα is widely expressed in human
tissues, controlling migration, proliferation, and apo-
ptosis , and mutations in the receptor play a role in
the generation of human malignancies, notably in the
pathogenesis of gastrointestinal stromal tumors , lung
tumors , and ovarian carcinoma . PDGFRαα sig-
naling through the fibroblast primary cilium or compa-
rable pathways in the primary cilium in other tissues
may be important in tissue homeostasis whereas per-
turbations in this pathway could lead to oncogenesis.
Supplemental Data include Supplemental Experimental Procedures
and two figures and are available with this article online at http://
This work was supported by the National Danish Research Council
[#21-02-0120, #21-01-0507, #21-04-0535] (S.T.C. and E.K.H.), the
Foundation of 1870 (S.T.C.), The NOVO Nordisk Foundation (L.S.),
by funds from the Albert Einstein College of Medicine (P.S.), and
from the US National Institutes of Health [GM-60992] (G.J.P.). Anti-
β-actin was a kind gift from Dr. Rønnov-Jessen (IMBF, The August
Krogh Building, University of Copenhagen, Denmark).
Received: May 6, 2005
Revised: September 1, 2005
Accepted: September 1, 2005
Published: October 25, 2005
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