TSH and cAMP do not signal mitogenesis through Ras activation.
Ras activation by receptor tyrosine kinases or serpentine receptors is generally considered to be essential for G1 phase progression and mitogenesis. In the physiologically relevant model of primary dog thyrocytes, the accumulation of the GTP-bound form of Ras constituted an early convergence point of various mitogenic or comitogenic stimuli including EGF, HGF, phorbol esters, insulin and carbachol. By contrast, the basal level of GTP-Ras was slightly reduced by TSH and forskolin and did not increase during the TSH/cAMP-dependent progression into G1 phase. This rules out a role for the activation of Ras as a signal in the mitogenesis elicited by TSH via cAMP in these cells.
Van Keymeulen
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Institute of Interdisciplinary Research (IRIBHN), Université Libre de Bruxelles, Campus Erasme, 808 Route de Lennik, Brussels, B-1070, Belgium. avkeymeu@ulb.ac.be
Roger
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Dumont
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JE
Dremier
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D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism / Q000494:pharmacology*; D004285:Dogs; D004789:Enzyme Activation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D008934:Mitogens / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D013972:Thyrotropin / Q000494:pharmacology*; D013997:Time Factors; D018631:ras Proteins / Q000378:metabolism*
D007328:Insulin; D008934:Mitogens; D005576:Colforsin; D004815:Epidermal Growth Factor; D017228:Hepatocyte Growth Factor; D006160:Guanosine Triphosphate; D002217:Carbachol; D013972:Thyrotropin; D000242:Cyclic AMP; D018631:ras Proteins; D000262:Adenylyl Cyclases; D013755:Tetradecanoylphorbol Acetate