Expression of GTP-binding proteins and prostaglandin E2 receptors during human T cell activation.
GTP-binding proteins (G-proteins) are a family of closely related, yet structurally distinct signal transducing proteins. In this study the presence and relative abundance of several G-proteins and of their corresponding mRNAs were measured in resting and activated human T lymphocytes. We found that T lymphocytes contain RNA coding for Gs, Gi2, and Gi3. No Gi1- and Go-specific RNA could be detected. Membrane fractions of resting and activated lymphocytes were studied in immunoblot experiments. Again, Gs, Gi2, and Gi3, but not Gi1 and Go, were detected. Upon mitogenic activation, a relative increase in mRNA for Gs and Gi3, but not for Gi2 could be demonstrated in Northern blot experiments. Immunoblotting indicated an increase in Gs and Gi3 density in membrane fractions of T cells as well. Paralleling the increase in Gs, we found that activated T cells produce five to seven times more cAMP per cell in response to prostaglandin E2 (PGE2) than resting lymphocytes. Finally, PGE2 binding studies showed that the number of receptors for this hormone increased from 435 +/- 322 to 1035 +/- 357 per cell following in vitro stimulation. We propose that in vitro T cell activation is paralleled by an increase in sensitivity to PGE2-induced cAMP generation. This sensitization is accompanied by both an increase in cell surface PGE2 receptor numbers as well as by increased expression of the signal transducing protein Gs and may physiologically be important for limiting an immune response.
Holter
W
W
Institute of Immunology-Vienna Int. Research Coop. Center (VIRCC), University of Vienna, Austria.
Spiegel
A M
AM
Howard
B H
BH
Weber
S
S
Brann
M R
MR
D000242:Cyclic AMP / Q000032:analysis; D019204:GTP-Binding Proteins / Q000032:analysis* / Q000235:genetics; D006801:Humans; D015151:Immunoblotting; D008213:Lymphocyte Activation; D012333:RNA, Messenger / Q000032:analysis; D011982:Receptors, Prostaglandin / Q000032:analysis*; D018078:Receptors, Prostaglandin E; D013601:T-Lymphocytes / Q000737:chemistry* / Q000276:immunology
D012333:RNA, Messenger; D011982:Receptors, Prostaglandin; D018078:Receptors, Prostaglandin E; D000242:Cyclic AMP; D019204:GTP-Binding Proteins