Linked Life Data

11916978

Source:http://linkedlifedata.com/resource/pubmed/id/11916978

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
23
pubmed:dateCreated
2002-6-3
pubmed:abstractText
The phosphorylation state of Ser(183) in the cytoplasmic tail of syndecan-4 determines the binding affinity of the cytoplasmic tail to phosphatidylinositol 4,5-bisphosphate (PIP(2)), the capacity of the tail to multimerize, and its ability to activate protein kinase C (PKC) alpha. We sought to identify the kinase responsible for this phosphorylation and to determine its downstream effects on PKCalpha activity and on endothelial cell function. Among several PKC isoenzymes tested, only PKCalpha and -delta were able to specifically phosphorylate Ser(183) in vitro. However, studies in cultured endothelial cells showed that the phosphorylation level of syndecan-4 was significantly reduced in endothelial cells expressing a dominant negative (DN) PKCdelta but not a DN PKCalpha mutant. Syndecan-4/PIP(2)-dependent PKCalpha activity was significantly increased in PKCdelta DN cells, while PKCdelta overexpression was accompanied by decreased PKCalpha activity. PKCdelta-overexpressing cells exhibited a significantly lower proliferation rate and an impaired tube formation in response to FGF2, which were mirrored by similar observations in PKCalpha DN endothelial cells. These findings suggest that PKCdelta is the kinase responsible for syndecan-4 phosphorylation, which, in turn, attenuates the cellular response to FGF2 by reducing PKCalpha activity. The reduced PKCalpha activity then leads to impaired endothelial cell function. We conclude that PKCdelta regulates PKCalpha activity in a syndecan-4-dependent manner.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
7
pubmed:volume
277
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
20367-71
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Protein kinase C (PKC) delta regulates PKCalpha activity in a Syndecan-4-dependent manner.
pubmed:affiliation
Angiogenesis Research Center and Section of Cardiology, Dartmouth-Hitchcock Medical Center, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't