INVESTIGADORES
REY Osvaldo
artículos
Título:
Neurotensin induces protein kinase C-dependent protein kinase D activation and DNA synthesis in human pancreatic carcinoma cell line PANC-1
Autor/es:
GUHA S, REY O, ROZENGURT E
Revista:
CANCER RESEARCH
Editorial:
AMER ASSOC CANCER RESEARCH
Referencias:
Año: 2002 p. 1632 - 1640
ISSN:
0008-5472
Resumen:
Signal transduction pathways through protein kinase C (PKC) may play a
significant role in DNA synthesis and proliferation of human pancreatic
cancers. Treatment of human pancreatic ductal adenocarcinoma cell line
PANC-1 with biologically active phorbol-12,13-dibutyrate led to
striking activation of protein kinase D (PKD), a member of a novel
family of serine/threonine kinases distinct from PKC isoforms. Using
PANC-1 as a model system, we demonstrate that neurotensin (NT) induced
a rapid and striking activation of PKD as determined by in vitro kinase
assay and by in vivo phosphorylation of serines 744, 748, and 916. PKD
activation induced by NT was abrogated by treatment of PANC-1 cells
with PKC inhibitors GF-1 and Ro 31-8220. NT induced a rapid and
transient translocation of PKD from the cytosol to the plasma membrane.
Inhibiting PKC activity blocked the reverse translocation of PKD from
the plasma membrane to the cytosol. Finally, we show that NT-induced
DNA synthesis in PANC-1 cells is PKC-dependent. Collectively our
results demonstrate, for the first time, the existence of a functional
PKC/PKD signaling pathway in human ductal pancreatic carcinoma cells
and suggest that PKCs mediate the mitogenic signaling process initiated
by NT.