The TSH receptor is linked with AP1 and NFkappaB signaling in COS7 cells.

In addition to it's classic coupling to Gs and Gq the TSHR was shown to also couple to further members of four G-protein families in membranes: G(s), G(q/11), G(i/0) and G(12/13). Moreover, GPCRs are able to stimulate mitogenic signaling pathways by switching the receptor coupling to different G-proteins or by interacting with scaffold proteins like beta-arrestins. These findings lead to the assumption of additional mitogenic TSHR stimulated signaling pathways. Therefore, we systematically investigated whether the TSH receptor is able to stimulate signaling pathways apart from the known cAMP and IP pathways. We used a luciferase reporter gene assay containing response elements covering a variety of signal transduction pathways. After TSH-stimulation the TSHR showed a significantly increased CRE-, AP1- or NFkappaB-mediated luciferase accumulation in COS7 cells. No effect on luciferase accumulation was found for the other reporter gene vectors. These findings lead to the hypothesis of a possible relevance of AP1 and NFkappaB for TSHR-dependent signaling pathways in COS cells which act in addition to the known cAMP and IP pathways.