Linked Life Data

8999881

Source:http://linkedlifedata.com/resource/pubmed/id/8999881

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1997-2-13
pubmed:abstractText
In the rat liver epithelial cell lines GN4 and WB, angiotensin II (Ang II) activates the Gq class of regulatory G-proteins, increasing intracellular calcium, protein kinase C activity, and protein tyrosine phosphorylation. We compared the ability of Ang II and other compounds that increase intracellular calcium (i.e. the calcium ionophore A23187 and thapsigargin) or protein kinase C activity (the phorbol ester 12-O-tetradecanoylphorbol-13-acetate) to activate p70 ribosomal S6 kinase (p70(S6K)) and p90 ribosomal S6 kinase (p90(RSK)). In GN4 cells, increasing intracellular calcium stimulated p70(S6K) activity in a rapamycin- and wortmannin- sensitive manner, but did not affect p90(RSK) activity. In contrast, 12-O-tetradecanoylphorbol-13-acetate strongly activated p90(RSK) but only weakly stimulated p70(S6K). The ability of calcium to activate p70(S6K) was confirmed by blocking the A23187-dependent activation through chelation of extracellular calcium with EGTA; the effect of thapsigargin was inhibited by the cell permeant chelator bis-(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetraacetoxymethyl ester (BAPTA-AM). Similarly, BAPTA-AM prevented the activation of p70(S6K) by Ang II, suggesting that this signal was largely calcium-dependent. In contrast, the Ang II-dependent activation of mitogen-activated protein kinase and p90(RSK) was not inhibited but was enhanced by BAPTA-AM. These results show that in GN4 cells, Ang II selectively activates p70(S6K) through effects on calcium, p90(RSK) through effects on protein kinase C. The activation of p70(S6K) by calcium stimuli or Ang II was independent of calmodulin but correlated well with the activation of the recently identified, nonreceptor calcium-dependent tyrosine kinase (CADTK)/PYK-2. Both calcium- and Ang II-dependent activation of p70(S6K) were attenuated by the tyrosine kinase inhibitor genistein, and activation of p70(S6K) was higher in GN4 than WB cells, correlating with the increased expression and activation of CADTK/PYK-2 in GN4 cells. In summary, these results demonstrate that intracellular calcium selectively activates p70(S6K) in GN4 cells, consistent with increased CADTK/PYK-2 signaling in these cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
17
pubmed:volume
272
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1920-8
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
An intracellular calcium signal activates p70 but not p90 ribosomal S6 kinase in liver epithelial cells.
pubmed:affiliation
Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina 27599-7295, USA. lmg@med.unc.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't