On the mechanism of cytosolic phospholipase A2 activation in CHO cells carrying somatostatin receptor: wortmannin-sensitive pathway to activate mitogen-activated protein kinase.
We examined the mechanism of arachidonate release induced by somatostatin-14 (SS14) in CHO-K1 cells overexpressing rat hippocampal somatostatin receptor SSTR4. SSTR4 couples to pertussis toxin (PTX)-sensitive G-protein in CHO cells and does not lead to phosphoinositides breakdown or intracellular calcium ([Ca2+]i) mobilization (Bito et al.: J. Biol. Chem. 269, 12722-12730, 1994). SSTR4 activated mitogen-activated protein (MAP) kinase and induced the phosphorylation of 85kDa cytosolic phospholipase A2 (cPLA2), in a PTX-sensitive manner. Furthermore, activations of both MAP kinase and cPLA2 were inhibited by treatment with wortmannin, at almost identical IC50 values. Thus, SSTR4 appears to stimulate MAP kinase and cPLA2 in a Gi-dependent, and through a wortmannin-sensitive pathway. We also showed that stimulation with SS14, in combination with calcium-ionophore, strongly enhanced arachidonate release from these cells.
Sakanaka
C
C
Department of Biochemistry, Faculty of Medicine, University of Tokyo, Japan.
Ferby
I
I
Waga
I
I
Bito
H
H
Shimizu
T
T
D000730:Androstadienes / Q000494:pharmacology*; D000818:Animals; D016466:CHO Cells; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006224:Cricetinae; D003600:Cytosol / Q000201:enzymology; D004789:Enzyme Activation; D019950:Mitogen-Activated Protein Kinase 1; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054467:Phospholipases A2; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017481:Receptors, Somatostatin / Q000378:metabolism*; D011994:Recombinant Proteins; D015398:Signal Transduction; D000077191:Wortmannin
D000730:Androstadienes; D017481:Receptors, Somatostatin; D011994:Recombinant Proteins; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D010741:Phospholipases A; D054467:Phospholipases A2; D000077191:Wortmannin