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Little is known about the relative role of cAMP-dependent protein kinase (cAPK) and guanine exchange factor directly activated by cAMP (Epac) as mediators of cAMP action. We tested cAMP analogs for ability to selectively activate Epac1 or cAPK and discriminate between the binding sites of Epac and of cAPKI and cAPKII. We found that commonly used cAMP(More)
TSH, mainly acting through cAMP, is the principal physiological regulator of thyroid gland function, differentiation expression, and cell proliferation. Both cAMP-dependent protein kinases [protein kinase A (PKA)] and the guanine-nucleotide-exchange factors for Rap proteins, exchange proteins directly activated by cAMP (Epac) 1 and Epac2, are known to(More)
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)(More)
In different systems, cyclic adenosine monophosphate (cAMP) either blocks or promotes cell cycle progression in mid to late G1 phase. Dog thyroid epithelial cells in primary culture constitute a model of positive control of DNA synthesis initiation and G0-S prereplicative phase progression by cAMP as a second messenger for thyrotropin (TSH). The(More)
Cell regulation and signal transduction are becoming increasingly complex, with reports of new cross-signalling, feedback, and feedforward regulations between pathways and between the multiple isozymes discovered at each step of these pathways. However, this information, which requires pages of text for its description, can be summarized in very simple(More)
The literature on intracellular signal transduction presents a confusing picture: every regulatory factor appears to be regulated by all signal transduction cascades and to regulate all cell processes. This contrasts with the known exquisite specificity of action of extracellular signals in different cell types in vivo. The confusion of the in vitro(More)
TTF-1 is a homeodomain-containing transcription factor mainly expressed in the thyroid where it controls the tissue-specific expression of the thyroglobulin, thyroperoxidase and TSH receptor genes. It is therefore potentially implicated in the hormonal control exerted by thyrotropin via the second messenger cyclic AMP on the transcription of these genes in(More)
Thyrotropin, through a cAMP-dependent pathway, stimulates function, differentiation, and proliferation of dog and human thyroid cells. Our previous findings suggested that, in addition to PKA activation, another cAMP-dependent mechanism is involved in TSH action. In this work, we assess whether the newly identified cAMP-Epac-Rap1 cascade is involved in(More)
Apoptosis, a physiological cell death, has been shown to be involved in tissue homeostasis as well as in tissue regression due to hormone deprivation. The cell population slowly turns over, with cell loss compensating mitogenicity. In the absence of thyrotropin, the cell population decreases. The possible involvement of apoptosis in this loss has been(More)