Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:4.6.1.1 (
adenylate cyclase
)
19,190
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The Janus kinase, JAK3 plays an important role in interleukin-2 (IL-2)-dependent signal transduction and proliferation of T lymphocytes. Our findings show that prostaglandin E2 (PGE2) can inhibit upregulation of JAK3 protein in naive T cells and can downregulate its expression in primed cells. Reduction in JAK3 was selective because expression of other tyrosine kinases (JAK1, p56(lck), and
p59(fyn)
) and signal transducer and activator of transcription (STAT)5, which are linked to IL-2 receptor (IL-2R) signaling pathway, were not affected. Inhibition of JAK3 may be controlled by intracellular cyclic adenosine monophosphate (cAMP) levels, as forskolin, a direct activator of
adenylate cyclase
and dibutyryl cAMP (dbcAMP), a membrane permeable analogue of cAMP suppressed JAK3 expression. Moreover, 3-isobutyl-1-methylxanthine (IBMX), an inhibitor of cAMP phosphodiesterase, potentiated PGE2-induced suppression of JAK3. In naive T cells, but not primed T cells, PGE2 and other cAMP elevating agents also caused a modest reduction in surface expression of the common gamma chain (gammac) that associates with JAK3. The absence of JAK3, but not IL-2R in T cells correlated with impaired IL-2-dependent signal transduction and proliferation. The alteration in IL-2 signaling included decreased tyrosine phosphorylation and DNA binding activity of STAT5 and poor induction of the c-Myc and c-Jun pathways. In contrast, IL-2-dependent induction of Bcl-2 was unaffected. These findings suggest that suppression of JAK3 levels may represent one mechanism by which PGE2 and other cAMP elevating agents can inhibit T-cell proliferation.
...
PMID:Downregulation of JAK3 protein levels in T lymphocytes by prostaglandin E2 and other cyclic adenosine monophosphate-elevating agents: impact on interleukin-2 receptor signaling pathway. 1009 Sep 41
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.
...
PMID:PGE(2)-mediated inhibition of T cell p59(fyn) is independent of cAMP. 1044 7
