Research

A kinase anchoring proteins and the small GTPases of the Rho family

A large number of agonists, including hormones and transmitters, activate their cognate receptors on the surface of cells, thereby stimulating the synthesis of the second messenger cyclic adenosine monophosphate (cAMP). Cyclic AMP activates protein kinase A (PKA) which modulates the activity of its effectors by phosphorylation of consensus sites. As PKA and many of its substrates are present throughout the cell, it is unclear how a raise of cAMP and the subsequent activation of PKA elicits a timely and spatially orchestrated cellular response. One mechanism is the compartmentalization of PKA, mediated by A-kinase anchoring proteins (AKAPs), a family of distinct but functionally conserved proteins. AKAP-mediated tethering of PKA to subcellular compartments is thought to localize PKA to specific sites and limit its access to a subset of substrates.

The main interest of our group is to identify and characterize AKAPs involved in cAMP-regulated processes such as arginine-vasopressin (AVP)-mediated water reabsorption, contraction of cardiomyocytes, renin-, proton- and insulin secretion.
Dysregulation of the cAMP-regulated processes leads to diseases including congenital and acquired nephrogenic diabetes insipidus, hypertension, gastric ulcers, diabetes mellitus and heart disease. The pharmacological interference with the function of specific AKAPs may proof a suitable concept for the treatment of these diseases. We have, therefore, initiated the search for peptides and low molecular weight compounds to modulate the function of specific AKAPs. At present we focus on the AKAPs Ht31/Rt31, and a new splice variant of AKAP18, AKAP18delta, which we have identified.The main interest of our group is to identify and characterize AKAPs involved in cAMP-regulated processes such as arginine-vasopressin (AVP)-mediated water reabsorption, contraction of cardiomyocytes, renin-, proton- and insulin secretion.

Other major interests of the group are to elucidate the roles of phosphodiesterases, the cytoskeleton, and the small GTPases of the Rho family in the AVP-mediated water reabsorption.