Polycystin-1, the polycystic kidney disease 1 gene
product, has been implicated in several signaling complexes
that are known to regulate essential cellular
functions. We investigated the role of polycystin-1 in
Wnt signaling and activator protein-1 (AP-1) activation.
To this aim, a membrane-targeted construct encoding
the conserved C-terminal region of mouse polycystin-
1 reported to mediate signal transduction
activity was expressed in human embryonic and renal
epithelial cells. To ensure specificity and minimal cotransfection
effects, we focused our study on the endogenous
proteins that actually transduce the signals,
-catenin and T-cell factor/lymphoid-enhancing factor
for Wnt signaling and (phosphorylated) c-Jun, ATF2,
and c-Fos for AP-1. Our data indicate that the C-terminal
region of polycystin-1 activates AP-1 by inducing
phosphorylation and expression of at least c-Jun and
ATF2, whereas c-Fos was not affected. Under our
experimental conditions, polycystin-1 did not modulate
Wnt signaling. AP-1 activity was aberrant in
human autosomal dominant polycystic kidney disease
(ADPKD) renal cystic epithelial cells and in renal epithelial
cells expressing transgenic full-length polycystin-
1, resulting in decreased Jun-ATF and increased
Jun-Fos activity, whereas Wnt signaling remained unaffected.
Since our data indicate that aberrant polycystin-
1 expression results in altered AP-1 activity,
polycystin-1 may be required for adequate AP-1
activity
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