Systems Biology of the Kidney:

Kinase Signaling Networks in Kidney Diseases

Protein phosphorylation affects 30% of the proteome by defining the functional and structural plasticity of proteins. Phosphorylation is involved in almost all fundamental biological processes and controls the dissemination of the information carried by hormones and other extracellular signals. Protein phosphorylation regulates pathways that transmit, encode and integrate the numerous external and internal signals in different gene expression patterns and diverse physiological responses. It determines for example (i) where and when enzymes become active, (ii) how signal transduction pathways are spatially and temporally organized, (iii) when and where interactions with scaffold and anchoring proteins occur in distinct subcellular environments, (iv) whether movement of proteins into and out of these complexes occurs and thereby (v) temporally regulates numerous signaling events.

Members of our lab are interested in the dynamic assembly of protein complexes and their role in kidney pathobiology. We use phosphoproteomics technologies to identify and characterize novel phosphoSerine/Threonine/Tyrosine binding domains involved in cellular signal transduction networks. We have novel technologies that are based on phospho-peptide library screening that allow for the identification of novel phospho-specific protein interactions and protein complexes that play a role in cilia biology in the kidney, slit diaphragm signaling at the glomerular filtration barrier or in genetic or age-related kidney diseases.