Identification of ARAP3, a Novel PI3K Effector Regulating Both Arf and Rho GTPases, by Selective Capture on Phosphoinositide Affinity Matrices
| Autor: | A. McGregor, Len R. Stephens, Nicholas T. Ktistakis, Phillip T. Hawkins, Keith Davidson, Chris D. Ellson, Arpi Nazarian, Maria Manifava, Alicia Eguinoa, Mark E. Cooper, Andrew B. Holmes, Sonja Krugmann, John Coadwell, Hediye Erdjument-Bromage, Robert H. Michell, Paul Tempst, N. Risso, S. H. Ridley, Sophie Dove, Anita Grewal, Karen E. Anderson, Ze-Yi Lim, Peter Lipp, Gavin F. Painter, J.W. Thuring |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
rho GTP-Binding Proteins
GTPase-activating protein ADP ribosylation factor Swine Molecular Sequence Data Plasma protein binding Biology DNA-binding protein Mass Spectrometry Phosphatidylinositol 3-Kinases Cytosol Phosphatidylinositol Phosphates Leukocytes Animals Cloning Molecular Cytoskeleton Molecular Biology Adaptor Proteins Signal Transducing Effector ADP-Ribosylation Factors GTPase-Activating Proteins Signal transducing adaptor protein Proteins Cell Biology Recombinant Proteins Cell biology Biochemistry ADP-Ribosylation Factor 6 COS Cells Signal transduction Carrier Proteins Protein Binding Signal Transduction |
| Zdroj: | Molecular Cell. 9(1):95-108 |
| ISSN: | 1097-2765 |
| DOI: | 10.1016/s1097-2765(02)00434-3 |
| Popis: | We show that matrices carrying the tethered homologs of natural phosphoinositides can be used to capture and display multiple phosphoinositide binding proteins in cell and tissue extracts. We present the mass spectrometric identification of over 20 proteins isolated by this method, mostly from leukocyte extracts: they include known and novel proteins with established phosphoinositide binding domains and also known proteins with surprising and unusual phosphoinositide binding properties. One of the novel PtdIns(3,4,5)P3 binding proteins, ARAP3, has an unusual domain structure, including five predicted PH domains. We show that it is a specific PtdIns(3,4,5)P3/PtdIns(3,4)P2-stimulated Arf6 GAP both in vitro and in vivo, and both its Arf GAP and Rho GAP domains cooperate in mediating PI3K-dependent rearrangements in the cell cytoskeleton and cell shape. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|