Malfunctions within the Cbl interactome uncouple receptor tyrosine kinases from destructive transport.
Proteins of the Cbl family are adaptor molecules and ubiquitin ligases with major functions in the regulation, intracellular transport and degradation of receptor tyrosine kinases (RTKs). Due to this central role, mutations that cause malfunctions of Cbl or their associated proteins - termed the Cbl interactome - easily lead to the transformation of affected cells and eventually the development of cancer. This review intends to give an overview on the mechanisms of Cbl-mediated cell transformation in light of the dysregulated intracellular trafficking of RTKs.
Dikic
Ivan
I
Institute of Biochemistry II, Goethe University School of Medicine, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany.
Schmidt
Mirko H H
MHH
D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000818:Animals; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D021381:Protein Transport / Q000502:physiology; D050721:Proto-Oncogene Proteins c-cbl / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D050721:Proto-Oncogene Proteins c-cbl; D020794:Receptor Protein-Tyrosine Kinases