title: Identification of a Src kinase SH3 binding site in the C-terminal domain of the human ErbB2 receptor tyrosine kinase.
abstract: Overexpression of the ErbB2 receptor tyrosine kinase is associated with most aggressive tumors in breast cancer patients and is thus one of the main investigated therapeutic targets. Human ErbB2 C-terminal domain is an unstructured anchor that recruits specific adaptors for signaling cascades resulting in cell growth, differentiation and migration. Herein, we report the presence of a SH3 binding motif in the proline rich unfolded ErbB2 C-terminal region. NMR analysis of this motif supports a PPII helix conformation and the binding to Fyn-SH3 domain. The interaction of a kinase of the Src family with ErbB2 C-terminal domain could contribute to synergistic intracellular signaling and enhanced oncogenesis.
authors.affiliation: IMM, CNRS, Aix-Marseille Université, 31 chemin J. Aiguier, 13402 Marseille Cedex 20, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Bornet
authors.affiliation: LISM, CNRS UMR 7255, Aix-Marseille Université, 31 chemin J. Aiguier, 13402 Marseille Cedex 20, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Nouailler
authors.affiliation: IMM, CNRS, Aix-Marseille Université, 31 chemin J. Aiguier, 13402 Marseille Cedex 20, France.
authors.forename: Michaël
authors.initials: M
authors.lastname: Feracci
authors.affiliation: LISM, CNRS UMR 7255, Aix-Marseille Université, 31 chemin J. Aiguier, 13402 Marseille Cedex 20, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Sebban-Kreuzer
authors.affiliation: IMM, CNRS, Aix-Marseille Université, 31 chemin J. Aiguier, 13402 Marseille Cedex 20, France.
authors.forename: Deborah
authors.initials: D
authors.lastname: Byrne
authors.affiliation: LISM, CNRS UMR 7255, Aix-Marseille Université, 31 chemin J. Aiguier, 13402 Marseille Cedex 20, France.
authors.forename: Hubert
authors.initials: H
authors.lastname: Halimi
authors.affiliation: CRCM, CNRS UMR7258, Inserm U1068, Institut Paoli-Calmettes, Aix-Marseille Université, UM105, F-13009 Marseille, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Morelli
authors.affiliation: CRCM, CNRS UMR7258, Inserm U1068, Institut Paoli-Calmettes, Aix-Marseille Université, UM105, F-13009 Marseille, France.
authors.forename: Ali
authors.initials: A
authors.lastname: Badache
authors.affiliation: LISM, CNRS UMR 7255, Aix-Marseille Université, 31 chemin J. Aiguier, 13402 Marseille Cedex 20, France. Electronic address: guerlesquin@imm.cnrs.fr.
authors.forename: Françoise
authors.initials: F
authors.lastname: Guerlesquin
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001665:Binding Sites; D001943:Breast Neoplasms / Q000201:enzymology / Q000473:pathology; D045744:Cell Line, Tumor; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000737:chemistry* / Q000378:metabolism*; D018909:src Homology Domains; D019061:src-Family Kinases / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D010455:Peptides; D018719:Erb-b2 Receptor Tyrosine Kinases; D019061:src-Family Kinases; C011083:polyproline; C508053:ERBB2 protein, human
keywords: ErbB2; IDP; Proline rich motifs; SH3 domain and NMR spectroscopy; Src-kinase