title: A single PXXP motif in the C-terminal region of srGAP3 mediates binding to multiple SH3 domains.
abstract: The Slit-Robo GTPase-activating protein 3 (srGAP3) has been implicated in different critical aspects of neuronal development. These findings have mainly been based on the characterisation of the three conserved globular N-terminal domains, while the function of the C-terminal region (CTR) is still unknown. We show that this predicted unstructured region acts as an adaptor by binding to the endocytic proteins Amphiphysin, Endophilin-A2, Endophilin-A1, as well as the Ras signalling protein Grb2. All these interactions depend on a single proline-rich motif in the CTR and the Src-homology 3 domains of the binding partners. Via these interactions srGAP3 could link receptor signalling events to the endocytic machinery.
authors.affiliation: Max Planck Institute for Developmental Biology, Department of Protein Evolution, Spemannstr. 35, D-72076 Tübingen, Germany.
authors.forename: Silvia
authors.initials: S
authors.lastname: Wuertenberger
authors.affiliation: Max Planck Institute for Developmental Biology, Department of Protein Evolution, Spemannstr. 35, D-72076 Tübingen, Germany. Electronic address: yvonne.groemping@caesar.de.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Groemping
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D020816:Amino Acid Motifs; D004705:Endocytosis / Q000502:physiology*; D051380:GRB2 Adaptor Protein / Q000235:genetics / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D015398:Signal Transduction / Q000502:physiology*; D018909:src Homology Domains
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; D020690:GTPase-Activating Proteins; D009419:Nerve Tissue Proteins; C107640:SH3GL2 protein, human; C465659:SRGAP3 protein, human; C075637:amphiphysin
keywords: Isothermal titration calorimetry; Mental disorder GAP; Protein–protein interaction; SH3 domain (adaptor); WAVE-associated RacGAP protein