The Eps 8 protein coordinates EGF receptor signalling through Rac and traf ® cking through Rab 5

* Department of Experimental Oncology, European Institute of Oncology, 20141 Milan, Italy 2 Max Planck Institute for Molecular Cell Biology and Genetics, 01307 Dresden, c/o European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany § IFOM, The FIRC Institute for Molecular Oncology, 20134 Milan, Italy 3 Present address: Laboratory of Biological Chemistry, Medical School University of Ioannina, 45110 Ioannina, Greece

[1]  A. F. Neuwald,et al.  A shared domain between a spindle assembly checkpoint protein and Ypt/Rab-specific GTPase-activators. , 1997, Trends in biochemical sciences.

[2]  C. Betsholtz,et al.  EPS8 and E3B1 transduce signals from Ras to Rac , 1999, Nature.

[3]  N. Nomura,et al.  RN-tre specifically binds to the SH3 domain of eps8 with high affinity and confers growth advantage to NIH3T3 upon carboxy-terminal truncation. , 1996, Oncogene.

[4]  L. Minichiello,et al.  Eps8, a substrate for the epidermal growth factor receptor kinase, enhances EGF‐dependent mitogenic signals. , 1993, The EMBO journal.

[5]  A. Wittinghofer,et al.  GTPase-activating proteins: helping hands to complement an active site. , 1998, Trends in biochemical sciences.

[6]  R. G. Anderson.  The caveolae membrane system. , 1998, Annual review of biochemistry.

[7]  C. Piccoli,et al.  Isolation and characterization of e3B1, an eps8 binding protein that regulates cell growth , 1997, Oncogene.

[8]  Oliver Ullrich,et al.  GTPase activity of Rab5 acts as a timer for endocytic membrane fusion , 1996, Nature.

[9]  M. Zerial,et al.  Kinetics of Interaction of Rab5 and Rab7 with Nucleotides and Magnesium Ions* , 1996, The Journal of Biological Chemistry.

[10]  P. Pelicci,et al.  eps15 and eps15R are essential components of the endocytic pathway. , 1997, Cancer research.

[11]  P. Crespo,et al.  The small GTP-binding proteins Rac1 and Cdc42regulate the activity of the JNK/SAPK signaling pathway , 1995, Cell.

[12]  D. Gallwitz,et al.  Identification of the catalytic domains and their functionally critical arginine residues of two yeast GTPase‐activating proteins specific for Ypt/Rab transport GTPases , 1999, The EMBO journal.

[13]  M. Zerial,et al.  rab5 controls early endosome fusion in vitro , 1991, Cell.

[14]  N. Morrice,et al.  A novel role for Rab5–GDI in ligand sequestration into clathrin-coated pits , 1998, Current Biology.

[15]  Andrea Musacchio,et al.  A novel peptide–SH3 interaction , 1999, The EMBO journal.

[16]  R. Carbone,et al.  Eps8, a tyrosine kinase substrate, is recruited to the cell cortex and dynamic F-actin upon cytoskeleton remodeling. , 1998, Experimental cell research.

[17]  Marino Zerial,et al.  A Novel Rab5 GDP/GTP Exchange Factor Complexed to Rabaptin-5 Links Nucleotide Exchange to Effector Recruitment and Function , 1997, Cell.

[18]  G. Johnson,et al.  Direct Interaction between Ras and the Kinase Domain of Mitogen-activated Protein Kinase Kinase Kinase (MEKK1) (*) , 1995, The Journal of Biological Chemistry.

[19]  K. Kishan,et al.  The SH3 domain of Eps8 exists as a novel intertwined dimer , 1997, Nature Structural Biology.

[20]  C. Marshall,et al.  rho family GTPase activating proteins p190, bcr and rhoGAP show distinct specificities in vitro and in vivo. , 1993, The EMBO journal.

[21]  R. Rappuoli,et al.  The small GTP binding protein rab7 is essential for cellular vacuolation induced by Helicobacter pylori cytotoxin , 1997, The EMBO journal.

[22]  G. Carpenter,et al.  The carboxyl terminus of epidermal growth factor receptor/erbB-2 chimerae is internalization impaired. , 1993, Oncogene.

[23]  P. P. Di Fiore,et al.  Direct binding of eps8 to the juxtamembrane domain of EGFR is phosphotyrosine- and SH2-independent. , 1995, Oncogene.