Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.11 (AMPK)
 12,425 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The production of the thyroid hormones by the thyroid tissue is regulated by thyrotropin (TSH). TSH, through cAMP, enhances all steps of T3 and T4 synthesis, among which transcription of the genes encoding the precursor protein, thyroglobulin (TG) and the enzyme responsible for the iodination and coupling mechanisms, thyroperoxidase (TPO). Run-on transcription assays show that the kinetics of TG gene transcriptional activation by cAMP is slow (8 to 16 hours) in dog thyrocytes in primary culture, while it is rapid (1 hour) in dog thyroid slices. Activation is sensitive to cycloheximide, reflecting the need for ongoing protein synthesis. In contrast, stimulation of TPO gene transcription is rapid in both experimental systems and is not inhibited in the presence of cycloheximide. It is concluded that different regulatory mechanisms are implicated in the control of Tg and TPO gene transcription by cAMP. However, the stimulation of TG and TPO gene transcription are equally suppressed by inhibition of cAMP-dependent protein kinase, which suggests that both regulatory mechanisms involve protein phosphorylation.
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PMID:Distinct transcriptional effects of cAMP on 2 thyroid specific genes: thyroperoxidase and thyroglobulin. 217 Feb 61

Thyrotropin (TSH), via a cyclic AMP (cAMP)-dependent pathway, induces cytoplasmic retractions, proliferation, and differentiation expression in dog thyroid cells. The role of cAMP-dependent protein kinase (PKA) in the induction of these events was assessed by microinjection into living cells. Microinjection of the heat-stable inhibitor of PKA (PKI) inhibited the effects of TSH, demonstrating that activation of PKA was required in this process. Overexpression of the catalytic (C) subunit of PKA brought about by microinjection of the expression plasmid pC alpha ev or of purified C subunit itself was sufficient to mimic the cAMP-dependent cytoplasmic changes and thyroperoxidase mRNA expression but not to induce DNA synthesis and thyroglobulin (Tg) expression. The cAMP-dependent morphological effect was not observed when C subunit was coinjected with the regulatory subunit (RI or RII subunit) of PKA. To mimic the cAMP-induced PKA dissociation into free C and R subunits, the C subunit was coinjected with the regulation-deficient truncated RI subunit (RIdelta1-95) or with wild-type RI or native RII subunits, followed by incubation with TSH at a concentration too low to stimulate the cAMP-dependent events by itself. Although the cAMP-dependent morphology changes were still observed, neither DNA synthesis nor Tg expression was stimulated in these cells. Taken together, these data suggest that in addition to PKA activation, another cAMP-dependent mechanism could exist and play an important role in the transduction of the cAMP signal in thyroid cells.
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PMID:Activation of cyclic AMP-dependent kinase is required but may not be sufficient to mimic cyclic AMP-dependent DNA synthesis and thyroglobulin expression in dog thyroid cells. 934 36