The EGF receptor as central transducer of heterologous signalling systems

CAIR-1/BAG-3 forms an EGF-regulated ternary complex with phospholipase C-γ and Hsp70/Hsc70

“…Intracellular calcium concentrations are tightly regulated and are altered during transmembrane signaling events, such as those stimulated by growth factors, and also in response to cellular injury or stress (Berridge et al, 1998;Bukau and Horwich, 1998;Zwick et al, 1999). We have identi®ed an inhibitor of calcium in¯ux in nonexcitable cells, CAI (Felder et al, 1991;Gusovsky et al, 1993;Kohn et al, 1994a).…”

Metalloproteinases in hypertension and cardiac disease: differential expression and mutual regulation

“…Therefore, metalloproteinases represent a transduction point for multiple signaling systems and a molecular communication network that governs a great variety of physiological processes [15,54]. Two features make the GqPCR agonist → metalloproteinase → EGFR transactivation mechanism attractive from a therapeutic point of view are: (1) growth factor receptor transactivation is significant only when levels of the agonist are exceedingly high and (2) growth factor receptor transactivation seems to be a common response to multiple pro-hypertensive agonists.…”

“…Diverse conditions such as stress, diabetes, obesity, life style as well as environmental and genetic factors predispose to hypertension and cardiac remodeling, at least in part, through the excessive production of vasoconstrictive GqPCR agonists. These agonists bind to cognate receptors to activate phospholipase C. One of the actions of phospholipase C leads to the cell membrane assembly of the NADPH oxidase complex, which next generates reactive oxygen species (ROS) that activate multiple MMPs and ADAMs [15,16].…”

Metalloproteinases: key and common mediators of multiple GPCRs and candidate therapeutic targets in models of hypertensive cardiac disease

“…Transactivation of the EGFR can explain how and why agonists of vasoactive G-proteincoupled receptors (GPCRs) promote cancer cell growth and proliferation of cancer cells [17]. In arteries, EGFR transactivation is also mediated, at least in part, by metalloproteinases, such as MMP-2 and MMP-7, which are overexpressed or activated downstream of GPCRs including adrenoceptors, endothelin-1 and angiotensin II receptors.…”