cAMP regulation of IL-2 receptor expression. Selective modulation of the p75 subunit.
As previous experiments have shown that IL-2 activity is abrogated by cAMP, its effect on IL-2R expression by normal and leukemic T lymphocytes was evaluated in detail. The exposure of murine or human T cells to dibutyryl cAMP or the cAMP-elevating drug, forskolin, resulted in a decrease in high affinity IL-2 binding. Equilibrium binding analyses revealed that elevation of cAMP for 4 to 5 h produced a 40 to 50% decrease in the number of detectable receptors, whereas the affinity of the IL-2R interaction remained unchanged. The effect of cAMP could be attributed to a selective effect on the 75-kDa chain of the IL-2R (p75) subunit of the 55-kDa chain of the IL-2R/p75 heterodimer. The mechanism for the decreased expression of high affinity IL-2R appears to be due to a dual effect of cAMP, which functions to both increase the rate of IL-2R internalization, and to decrease the rate of expression of new receptors. Moreover, the effect of cAMP on IL-2 binding to p75 subunits is post-transcriptional, because the steady state levels of p75 mRNA expression are not altered within a time interval that produced nearly a 50% reduction in p75 binding.
Johnson
K W
KW
Dartmouth Medical School, Department of Medicine, Hanover, NH 03756.
Smith
K A
KA
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000032:analysis
D007376:Interleukin-2; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D005576:Colforsin; D003994:Bucladesine; D000242:Cyclic AMP