Crosstalk Between cAMP and Phosphoinositide System in Signal Transduction Pathways Through TSH Receptor.
- Author:
Byung Sool MOON
1
;
Young Joo PARK
;
Seong Yeon KIM
;
Bo Youn CHO
;
Hong Kyu LEE
;
Do Joon PARK
Author Information
1. Department of Internal Medicine, Seoul National University College of Medicine, Korea.
- Publication Type:Original Article
- Keywords:
Signal transduction;
TSH receptor;
G protein;
adenylate cyclase;
phospholipase C;
protein kinase A;
protein kinase C
- MeSH:
Adenylyl Cyclases;
Animals;
Colforsin;
Cyclic AMP-Dependent Protein Kinases;
GTP-Binding Proteins;
Inositol;
Phosphotransferases;
Protein Kinase C;
Rats;
Receptors, Thyrotropin*;
Signal Transduction*;
Staurosporine;
Thyroid Gland;
Type C Phospholipases
- From:Journal of Korean Society of Endocrinology
2003;18(4):404-413
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: TSH stimulates both the adenyl cyclase and phospholipase C (PLC) pathways by binding to a single cell surface receptor that is coupled to G protein, and we examined crosstalk between these two signaling pathways. METHODS: FRTL-5 rat thyroid cells were grown in 6H medium, then incubated with 5H medium before the stimulation. Then cells were incubated for 24 hours with 5H mix containing 1 mCi/L myo-(2-N-3H) inositol. After pretreatment of 100 microM Rp-cAMP, 100 microM forskolin, 50 nM staurosporine, or 100 nM PMA (phorbol-12-myristate-13-acetate), TSH were added in different experiments. After 30 min at 37 degrees C, cells were disrupted and IP formation was determined. RESULTS: Stimulation with 100 microU/mL TSH resulted in a 1.65 fold increase in IP generation. In pursuing the possibility that the two post-receptor events might be linked in some way, we examined the effect of exogenously administrated Rp-cAMP, protein kinase A antagonist, and forskolin, a direct stimulant of protein kinase A, on IP generation achieved at a dose of 100 microU/mL TSH. The pretreatment of 100 M Rp-cAMP at a concentration sufficient to inhibit protein kinase A enhanced TSH-induced IP production. This effect of Rp-cAMP was dose-dependent. Forskolin attenuatedTSH-stimulated increases in phosphatidylinositide turnover. PMA, a protein kinase C (PKC) activator and staurosporine, a PKC inhibitor did not affect TSH-induced IP generation. CONCLUSION: These data suggested that activation of adenylate cyclase/cAMP post-receptor signalling casacde, which results in the protien kinase A activation, has an inhibitory effect on IP turnover activated by TSH.
