Conformationally constrained analogs of diacylglycerol. Interaction of .gamma.-lactones with the phorbol ester receptor of protein kinase C

1992 ◽  
Vol 114 (3) ◽  
pp. 1059-1070 ◽  
Author(s):  
Kelly Teng ◽  
Victor E. Marquez ◽  
George W. A. Milne ◽  
Joseph J. Barchi ◽  
Marcelo G. Kazanietz ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Phorbol Ester ◽  
Conformationally Constrained ◽  
Kinase C ◽  
Phorbol Ester Receptor

ChemInform Abstract: Conformationally Constrained Analogues of Diacylglycerol. Interaction of γ-Lactones with the Phorbol Ester Receptor of Protein Kinase C.

ChemInform ◽  
2010 ◽  
Vol 23 (25) ◽  
pp. no-no
Author(s):  
K. TENG ◽  
V. E. MARQUEZ ◽  
G. W. A. MILNE ◽  
J. J. JUN. BARCHI ◽  
M. G. KAZANIETZ ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Phorbol Ester ◽  
Conformationally Constrained ◽  
Kinase C ◽  
Phorbol Ester Receptor

scholarly journals Characterization of the Rac-GAP (Rac-GTPase-activating protein) activity of β2-chimaerin, a ‘non-protein kinase C’ phorbol ester receptor

2003 ◽  
Vol 375 (2) ◽  
pp. 313-321 ◽  
Author(s):  
Maria Jose CALOCA ◽  
HongBin WANG ◽  
Marcelo G. KAZANIETZ
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Phorbol Ester ◽  
Phorbol Esters ◽  
Gtpase Activating Protein ◽  
Protein Activity ◽  
Rac Gtpase ◽  
Kinase C ◽  
Phorbol Ester Receptor

The regulation and function of β2-chimaerin, a novel receptor for the phorbol ester tumour promoters and the second messenger DAG (diacylglycerol), is largely unknown. As with PKC (protein kinase C) isoenzymes, phorbol esters bind to β2-chimaerin with high affinity and promote its subcellular distribution. β2-Chimaerin has GAP (GTPase-activating protein) activity for the small GTP-binding protein Rac1, but for not Cdc42 or RhoA. We show that acidic phospholipids enhanced its catalytic activity markedly in vitro, but the phorbol ester PMA had no effect. β2-Chimaerin and other chimaerin isoforms decreased cellular levels of Rac-GTP markedly in COS-1 cells and impaired GTP loading on to Rac upon EGF (epidermal growth factor) receptor stimulation. Deletional and mutagenesis analysis determined that the β2-chimaerin GAP domain is essential for this effect. Interestingly, PMA has a dual effect on Rac-GTP levels in COS-1 cells. PMA increased Rac-GTP levels in the absence of a PKC inhibitor, whereas under conditions in which PKC activity is inhibited, PMA markedly decreased Rac-GTP levels and potentiated the effect of β2-chimaerin. Chimaerin isoforms co-localize at the plasma membrane with active Rac, and these results were substantiated by co-immunoprecipitation assays. In summary, the novel phorbol ester receptor β2-chimaerin regulates the activity of the Rac GTPase through its GAP domain, leading to Rac inactivation. These results strongly emphasize the high complexity of DAG signalling due to the activation of PKC-independent pathways, and cast doubts regarding the selectivity of phorbol esters and DAG analogues as selective PKC activators.

The complete primary structure of protein kinase C--the major phorbol ester receptor

Science ◽  
1986 ◽  
Vol 233 (4766) ◽  
pp. 853-859 ◽  
Author(s):  
P. Parker ◽  
L Coussens ◽  
N Totty ◽  
L Rhee ◽  
S Young ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Phorbol Ester ◽  
Primary Structure ◽  
Kinase C ◽  
Phorbol Ester Receptor ◽  
Complete Primary Structure

scholarly journals Phorbol Esters and Related Analogs Regulate the Subcellular Localization of β2-Chimaerin, a Non-protein Kinase C Phorbol Ester Receptor

2001 ◽  
Vol 276 (21) ◽  
pp. 18303-18312 ◽  
Author(s):  
Maria J. Caloca ◽  
HongBin Wang ◽  
Andrew Delemos ◽  
Shaomeng Wang ◽  
Marcelo G. Kazanietz
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Subcellular Localization ◽  
Phorbol Ester ◽  
Phorbol Esters ◽  
Kinase C ◽  
Phorbol Ester Receptor
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