Role of the Different Mitogen-Activated Protein Kinase Subfamilies in the Stimulation of Dog and Human Thyroid Epithelial Cell Proliferation by Cyclic Adenosine 5′-Monophosphate and Growth Factors
| Autor: | Sandrine Perpete, Fabrice Vandeput, Jacques Emile Dumont, Katia Coulonval, Françoise Lamy |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
medicine.medical_specialty
Arsenites MAP Kinase Signaling System Pyridines medicine.medical_treatment p38 mitogen-activated protein kinases Thyroid Gland Thyrotropin p38 Mitogen-Activated Protein Kinases chemistry.chemical_compound Dogs Endocrinology Epidermal growth factor Internal medicine Cyclic AMP medicine Animals Humans Hypoglycemic Agents Insulin Enzyme Inhibitors Phosphorylation Protein kinase B Cells Cultured Flavonoids Forskolin Epidermal Growth Factor biology Hepatocyte Growth Factor Kinase Growth factor Colforsin Imidazoles Epithelial Cells Sodium Compounds chemistry Mitogen-activated protein kinase Carcinogens biology.protein Tetradecanoylphorbol Acetate Hepatocyte growth factor Mitogen-Activated Protein Kinases Cell Division medicine.drug |
| Zdroj: | Endocrinology. 144:1341-1349 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/en.2001-211316 |
| Popis: | We have investigated the role of the different classes of MAPKs, i.e. ERKs, c-Jun N-terminal kinases (JNKs), and p38 MAPK in the proliferation of dog and human thyroid epithelial cells (thyrocytes) in primary cultures. In these cells, TSH, acting through cAMP, epidermal growth factor, hepatocyte growth factor (HGF), and phorbol 12-myristate 13-acetate induce DNA synthesis. With the exception of HGF, all of these factors require the presence of insulin for mitogenic effects to be expressed.We found that TSH and forskolin are without effect on the phosphorylation and activity of the different classes of MAPKs. In contrast, all the cAMP-independent growth factors, whereas without effect on the phosphorylation and activity of JNKs and p38 MAPK, stimulated the ERKs. This effect was strong and sustained in response to HGF, epidermal growth factor and 12-myristate 13-acetate but weak and transient in response to insulin. Moreover, whereas in stimulated cells DNA synthesis was inhibited by PD 098059, an inhibitor of MAPK kinase 1 and consequently of ERKs, it was not modified by SB 203580, an inhibitor of p38 MAPK.Taken together, these data 1) exclude a role of JNKs and p38 MAPK in the proliferation of dog and human thyrocytes; 2) suggest that the mitogenic action of the cAMP-independent agents requires a strong and sustained activation of both ERKs and phosphatidylinositol 3-kinase/protein kinase B as realized by HGF alone or by the other agents together with insulin; and 3) show that TSH and cAMP do not activate ERKs but that the weak activation of ERKs by insulin is nevertheless necessary for DNA synthesis to occur. |
| Databáze: | OpenAIRE |
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