Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2002-3-25
pubmed:abstractText
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
62
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1632-40
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Neurotensin induces protein kinase C-dependent protein kinase D activation and DNA synthesis in human pancreatic carcinoma cell line PANC-1.
pubmed:affiliation
Department of Medicine, Division of Digestive Diseases, School of Medicine and Molecular Biology Institute, University of California, Los Angeles, California 90095, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't