title: The role of small adaptor proteins in the control of oncogenic signalingr driven by tyrosine kinases in human cancer.
abstract: Protein phosphorylation on tyrosine (Tyr) residues has evolved as an important mechanism to coordinate cell communication in multicellular organisms. The importance of this process has been revealed by the discovery of the prominent oncogenic properties of tyrosine kinases (TK) upon deregulation of their physiological activities, often due to protein overexpression and/or somatic mutation. Recent reports suggest that TK oncogenic signaling is also under the control of small adaptor proteins. These cytosolic proteins lack intrinsic catalytic activity and signal by linking two functional members of a catalytic pathway. While most adaptors display positive regulatory functions, a small group of this family exerts negative regulatory functions by targeting several components of the TK signaling cascade. Here, we review how these less studied adaptor proteins negatively control TK activities and how their loss of function induces abnormal TK signaling, promoting tumor formation. We also discuss the therapeutic consequences of this novel regulatory mechanism in human oncology.
authors.affiliation: CNRS UMR5237, University Montpellier, CRBM, Montpellier, France.|Present address: INSERM U1016, CNRS UMR8104, Institut Cochin, Paris, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Naudin
authors.affiliation: CNRS UMR5237, University Montpellier, CRBM, Montpellier, France.|Present address: SFR Biosit (UMS CNRS 3480/US INSERM 018), MRic Photonics Platform, University Rennes, Rennes, France.
authors.forename: Clément
authors.initials: C
authors.lastname: Chevalier
authors.affiliation: CNRS UMR5237, University Montpellier, CRBM, Montpellier, France.|Equipe Labellisée LIGUE 2014, Ligue Contre le Cancer, Paris, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Roche
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D011505:Protein-Tyrosine Kinases
keywords: adaptor proteins; cancer therapy; cell signaling; human cancer; tyrosine kinase