© 1996 American Heart Association, Inc.
Articles |
Endothelial Cell Tyrosine Kinase Receptor and G Protein–Coupled Receptor Activation Involves Distinct Protein Kinase C Isoforms
From the Franz Volhard Clinic, Virchow Klinikum at the Max Delbrück Center for Molecular Medicine, Humboldt University of Berlin, Berlin, Germany.
Correspondence to Hermann Haller, MD, Franz-Volhard-Klinik, Wiltberg Strasse 50, 13122 Berlin, Germany.
Abstract Protein kinase C (PKC) is a family of
serine/threonine protein kinase isoforms that is important to
intracellular enzymes for both tyrosine kinase receptors and G
protein–coupled receptors. However, which isoforms are linked to
which class of receptors in endothelial cell signaling
is not known. Moreover, the PKC isoforms in endothelial
cells have not been thoroughly characterized. We tested the hypothesis
that specific PKC isoforms are involved in different signaling
pathways. PKC isoform expression was assessed by using reverse
transcription polymerase chain reaction and Western blotting. The
spatial distribution of PKC after stimulation of the cells with basic
fibroblast growth factor (bFGF) and thrombin was examined by using
confocal microscopy. Expression of PKC 
, 
, 
, 
, and 
was
detectable on both the mRNA and protein levels. In resting cells, PKC
and were mostly distributed in the cytosol, while PKC and
were also present in the nucleus. Nuclear immunoreactivity of
PKC and increased significantly between passages 1 and 3. The
phorbol ester TPA induced a rearrangement of PKC and a
translocation of PKC and to the nucleus. Treatment of
endothelial cells with TPA for 24 hours caused PKC ,
, and to disappear, while PKC was not influenced by TPA.
bFGF induced a rapid assembly of PKC along cytosolic structures,
followed by a translocation of the isoform toward the perinuclear
region and into the nucleus. bFGF had a similar effect on PKC . In
contrast, thrombin had a smaller effect on nuclear translocation of PKC
, did not influence PKC , and induced a rapid nuclear
translocation of PKC . Thus, tyrosine kinase receptor activation via
bFGF induced a rapid association of PKC and with nuclear
structures, while activation of the G protein–coupled thrombin
receptor increased mostly nuclear PKC . The translocation of PKC
isoforms into the nucleus by growth-promoting factors may be
important for the induction of endothelial cell growth.
Key Words: tyrosine kinase receptors • protein kinase C isoforms • endothelial cells • thrombin • basic fibroblast growth factor
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