Proposed model for b2-AR- and prostanoid-receptor-mediated PLC and calcium signalling. Receptors coupling to Gs stimulate AC, resulting in elevated cAMP levels and activation of Epac1. Epac1 then catalyses GTP-loading on Rap2B, which leads to PLC-e activation. The proposed pathway may involve additional signalling components to attain PLC stimulation.The action of cAMP seems to be independent of PKA; Instead, the cAMP-activated Rap-GEF Epac seems to serve as a cAMP effector, inducing GTP loading and, hence, activation of Rap2B, which then leads to specific activation of PLC-e, which has been shown to interact with Rap GTPases.It is an attractive hypothesis, therefore, that the Rap-dependent PLC and calcium signalling pathway reported here is not restricted to Gs-and AC-coupled receptors, such as the b2-AR and the prostanoid receptor, but could be used by other receptors as well.
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REFERENCES: Schmidt Martina, et al (2001) A new phospholipse-C-calcium signalling pathway mediated by cyclic AMP and a Rap GTPase. Nature Cell Biol. Vol 3, 1020-24