个人简介

Doctoraal, University of Amsterdam, 1987; Ph.D. University of Amsterdam, The Netherlands, 1993; Postdoctoral Research, The Salk Institute, 1993-1994; Postdoctoral Research, Samuel Lunenfeld Research Institute, 1994-1997; UCSD, 1997-2005.

研究领域

Biochemistry

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.

近期论文

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Murphy, Brian M.; Swarts, Spencer; Mueller, Barbara M.; et al., Protein instability following transport or storage on dry ice Nature Methods 2013, 10 278-279. Oku, Shinichiro; van der Meulen, Talitha; Copp, Jeremy; et al., Engineering NGF receptors to bind Grb2 directly uncovers differences in signaling ability between Grb2-and ShcA-binding sites FEBS Letters 2012, 586 3658-3664. Guttman M, Betts GN, Barnes H, et al., Interactions of the NPXY microdomains of the low density lipoprotein receptor-related protein 1 Proteomics 2009, 9 5016-5028. Glenn G, van der Geer P, Toll-like receptors stimulate regulated intramembrane proteolysis of the CSF-1 receptor through Erk activation FEBS Letters 2008, 582 911-915. Betts GN, van der Geer P, Komives EA, Structural and functional consequences of tyrosine phosphorylation in the LRP1 cytoplasmic domain Journal of Biological Chemistry 2008, 283 15656-15664. Glenn G, van der Geer P, CSF-1 and TPA stimulate independent pathways leading to lysosomal degradation or regulated intramembrane proteolysis of the CSF-1 receptor FEBS Letters 2007, 581 5377-5381. Wiley SE, Paddock ML, Abresch EC, et al., The outer mitochondrial membrane protein mitoNEET contains a novel redox-active 2Fe-2S cluster Journal of Biological Chemistry 2007, 282 23745-23749.