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Fig. 5 | BMC Cancer

Fig. 5

From: Protein Kinase A-induced tamoxifen resistance is mediated by anchoring protein AKAP13

Fig. 5

Model for PKA-mediated ERαS305 phosphorylation and the role of AKAP13 in this process. AKAP13 interacts with ERα as well as PKA-RII. This way, AKAP13 functions as a scaffolding protein, bringing together the PKA complex and its substrate, ERα. When members of the seven-transmembrane domain (7TM) receptors/ G protein-coupled receptors (GPCRs) are activated, this results in an activation of Adenyl Cyclase to generate cAMP. PKA is consequently activated, by the association of the PKA-regulatory subunits with cAMP. Subsequently, the catalytic subunit can dissociate from the complex and directly phosphorylate ERα at Serine 305. This phosphorylation at ERαS305P results in the recognition of tamoxifen as an ERα agonist, initiation of tamoxifen-driven gene transcription and consequently tamoxifen resistance

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