The Independent Young Researcher Group for Cardiovascular Signaling has emerged from the group of Prof. Werner Müller-Esterl, who continues his career as President of the Goethe University Frankfurt. We share a strong interest in the signaling cascades involved in regulating endothelial and vascular smooth muscle cell function. As a regulator of endothelial permeability, smooth muscle cell relaxation and of platelet adhesion, nitric oxide (NO) is one key messenger in vascular homeostasis (Fig. 1). Upon stimulation of endothelial cells, e.g. with bradykinin through the bradykinin receptor B2R and the consequent rise in intracellular Ca2+ levels, endothelial nitric oxide synthase (eNOS) is activated to produce NO. NO is a diffusible second messenger, which exerts many of its biological effects through the stimulation of the smooth muscle cell resident guanylyl cyclase (GC). GC converts GTP into the potent second messenger cGMP, which in turn activates protein kinase G to phosphorylate several downstream targets. Finally cGMP levels are decreased through the rapid conversion of cGMP to GMP by phosphodiesterases. We aim to understand the role of the two recently discovered proteins, NOSIP and NOSTRIN, in the elaborate protein network regulating NO synthase localization and activity.

Fig. 1. Molecular mechanisms governing the kinin-NO-cGMP pathway in mammalian cells