title: Defective downregulation of receptor tyrosine kinases in cancer.
abstract: Most growth factors control cellular functions by activating specific receptor tyrosine kinases (RTKs). While overactivation of RTK signalling pathways is strongly associated with carcinogenesis, it is becoming increasingly clear that impaired deactivation of RTKs may also be a mechanism in cancer. A major deactivation pathway, receptor downregulation, involves ligand-induced endocytosis of the RTK and subsequent degradation in lysosomes. A complex molecular machinery that uses the small protein ubiquitin as a key regulator assures proper endocytosis and degradation of RTKs. Here we discuss evidence that implicates deregulation of this machinery in cancer.
authors.affiliation: Department of Biochemistry, Norwegian Radium Hospital, Montebello, Oslo, Norway.
authors.forename: Kristi G
authors.initials: KG
authors.lastname: Bache
authors.forename: Thomas
authors.initials: T
authors.lastname: Slagsvold
authors.forename: Harald
authors.initials: H
authors.lastname: Stenmark
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism; D015536:Down-Regulation; D004705:Endocytosis / Q000502:physiology; D056827:Endosomal Sorting Complexes Required for Transport; D006801:Humans; D008024:Ligands; D008247:Lysosomes / Q000378:metabolism; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism*; D021381:Protein Transport; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism; D000099177:Tsg101 Protein
chemical_list: D004268:DNA-Binding Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D008024:Ligands; D020794:Receptor Protein-Tyrosine Kinases; D014157:Transcription Factors; D025801:Ubiquitin; D000099177:Tsg101 Protein