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Project 5

PIX proteins as regulators of receptor tyrosine kinase endocytosis and the actin cytoskeleton

Rho GTPases such as Rac1 and Cdc42 are well known for their function in regulating actin cytoskeletal dynamics in fibroblast and neuronal cells. Proteins modulating the activity of Rho GTPases include guanine nucleotide exchange factors (GEFs), such as the close homologues alpha- and betaPIX. Mutations in alphaPIX and other genes encoding regulator and effector proteins of Rho GTPases have been found in patients with mental retardation indicating that Rho GTPases play a pivotal role in neuronal morphogenesis and structural plasticity. In particular, betaPIX was found to modulate the activity state of the epidermal growth factor receptor (EGFR) by sequestering the E3 ubiquitin ligase Cbl from EGFR. Cbl proteins are required for monoubiquitylation and subsequent downregulation of EGFR. Since alphaPIX associates with Cbl, the main objective of our research project is to study the role of alphaPIX together with Cbl in EGFR ubiquitylation and actin cytoskeletal dynamics mediated by Rac1 and Cdc42 during endocytosis.

Contact:

Prof. Dr. rer. nat. Kerstin Kutsche
Institute of Human Genetics
University Medical Center Eppendorf (UKE)
Martinistraße 52
D-20246 Hamburg
Germany

Email: kkutsche@uke.uni-hamburg.de
Homepage: Research Group - Kerstin Kutsche

Dr. rer. nat. Georg Rosenberger
Institute of Human Genetics
University Medical Center Eppendorf (UKE)
Martinistraße 52
D-20246 Hamburg
Germany
Email: rosenberger@uke.uni-hamburg.de
Homepage: Research Group - Georg Rosenberger

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last update: Dieter Münch-Harrach, 24.02.2010