Integration of transmembrane signaling. Cross-talk among G-protein-linked receptors and other signal transduction pathways

The heart is a point of convergence for many transmembrane signal transduction pathways and, as such, exemplifies the complexities of sorting out their interactions. In the heart and cardiovascular system, hormone and neurotransmitter signals are propagated via G-protein-and non-G-protein-linked receptors. The receptors, in turn, are coupled to many effectors, including adenylylcyclases, phospholipases, and ion channels, as well as protein kinases and phosphatases. Integrating the information from numerous signaling pathways requires "cross-talk" among the different pathways. This article provides a perspective and attempts to describe in some detail what is known about a few of these interactions. Cross-talk from stimulatory to inhibitory adenylylcyclase pathways, from inhibitory to stimulatory adenylylcyclase pathways, from the adenylylcyclase to the phospholipase-C pathway, and from tyrosine kinase to G-protein-coupled receptors is described. Because of its central importance in the regulation of the cardiovascular system, and due to the availability of good model systems, the powerful responses mediated by the β-adrenergic receptor pathway serve as an excellent model to approach this subject.