PGE(2)-mediated inhibition of T cell p59(fyn) is independent of cAMP.
We recently observed that prostaglandin E(2) (PGE(2))-mediated suppression of T cell functions could result from an attenuation of p59(fyn) protein tyrosine kinase activity. The present study evaluated the effects of an adenylate cyclase agonist (forskolin) and antagonist (SQ-22536), as well as those of cAMP analogues (dibutyryl cAMP and 8-bromo- cAMP), on T cell p59(fyn) kinase activity. The study allowed us to assess whether PGE(2)-mediated activation of adenylate cyclase by itself or the elevation in intracellular cAMP levels is an integral event in the modulation of anti-CD3-linked p59(fyn) activation in T cells. The experiments were carried out with splenic T cells from male Sprague-Dawley rats. A 30-50% suppression in the autophosphorylation and the kinase activity of p59(fyn) in T cells incubated with PGE(2) or forskolin was observed. Pretreatment of T cells with SQ-22536 prevented significant PGE(2)-mediated inhibition of T cell p59(fyn) kinase activity. In contrast, no change in p59(fyn) autophosphorylation and kinase activity in T cells treated with cAMP analogues was observed. These data suggest that PGE(2)-mediated suppression of p59(fyn) autophosphorylation and kinase activity in T cells is dependent on the activation of adenylate cyclase and independent of the elevation in cAMP levels.
Choudhry
M A
MA
Trauma and Critical Care Research Labs, Departments of Surgery and Physiology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois 60153, USA.
Ahmed
Z
Z
Sayeed
M M
MM
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000502:physiology*; D015232:Dinoprostone / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors*; D051076:Proto-Oncogene Proteins c-fyn; D051381:Rats; D017207:Rats, Sprague-Dawley; D013601:T-Lymphocytes / Q000378:metabolism*
D000067956:Adenylyl Cyclase Inhibitors; D000906:Antibodies; D017252:CD3 Complex; D004791:Enzyme Inhibitors; D011518:Proto-Oncogene Proteins; C017759:9-(tetrahydro-2-furyl)-adenine; D005576:Colforsin; D000242:Cyclic AMP; C494961:Fyn protein, rat; D051076:Proto-Oncogene Proteins c-fyn; D000262:Adenylyl Cyclases; D000225:Adenine; D015232:Dinoprostone