Peter van der Geer, Ph.D.

In a multicellular organism, cells have to communicate with each other so that they can coordinate their activities. Cellular communication is usually mediated by extracellular messenger molecules that are recognized by receptors present on the surface of target cells. Binding of a messenger molecule to a receptor results in biochemical changes within the cell that make it possible for the cell to respond to the incoming message. Many different processes, such as cell division, differentiation, cell migration, metabolism, and cell death, are regulated in response to extracellular messenger molecules.

 

Signal transduction is the process that translates the binding of a messenger molecule to its receptor into changes in biochemistry, cytoskeletal structure, or gene transcription. Receptor protein-tyrosine kinases represent one class of receptors for extracellular messenger molecules. They contain an extracellular ligand-binding domain and a cytoplasmic protein kinase domain and are activated directly by the interaction with specific extracellular ligands. Activated receptors autophosphorylate on tyrosine residues and autophosphorylation sites act as binding-sites for specific cellular signaling proteins. Signaling proteins, which often contain SH2 or PTB domains, mediate the activation of cellular signal transduction cascades in response to receptor activation.

 

We are interested in signal transduction by protein-tyrosine kinases with particular emphasis on the role of signaling proteins in this process. Most recently we have focused on proteolytic processing of the CSF-1 receptor and the function of Shc and c-Cbl during protein-tyrosine kinase signaling.