Dissecting how receptor tyrosine kinases modulate G protein-coupled receptor function.

Receptor tyrosine kinases and G protein-coupled receptors modulate physiological processes and are also involved in the pathogenesis of some diseases. These receptors have intense bidirectional crosstalks leading to interactions in their signaling pathways and also modulation of the receptors themselves. In some cases, the receptor tyrosine kinases phosphorylate G protein-coupled receptors whereas in others phosphoinositide 3-kinase, protein kinase B and protein kinase C are key elements in these crosstalks. Two paracrine/ autocrine processes also participate, i.e., epidermal growth factor transactivation and sphingosine 1-phosphate generation and signaling. G proteins seem to mediate actions of receptor tyrosine kinases, but how this takes place is far from completely understood; some models are presented. Recent data indicate that the mitogen activated protein kinase cascade also mediate crosstalks. In the present perspective these processes are outlined using information from receptors that have been intensively studied, and important gaps in our knowledge are indicated.