The Cbl family: ubiquitin ligases regulating signaling by tyrosine kinases.
The Cbl proteins compose a family of ubiquitin ligases that play a central role in the down-regulation of signaling cascades involving receptor and nonreceptor tyrosine kinases. Analysis of the activity of these proteins suggests that they can regulate the signaling process through ubiquitination of the plasma membrane receptors and various downstream signaling components, including the Cbl proteins themselves. Structural analysis of the Cbl proteins shows that, in many instances, they interact with phosphorylated tyrosine residues on their targets. Furthermore, phosphorylation of specific tyrosine residues on the Cbl proteins may provide an additional level of control on the ubiquitinating activity of these proteins.
Sanjay
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Departments of Orthopaedics and Cell Biology and the Yale Cancer Center, Yale University School of Medicine, New Haven, CT 06520-8044, USA.
Horne
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Baron
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D000818:Animals; D003546:Cysteine Endopeptidases / Q000378:metabolism / Q000502:physiology; D008025:Ligases / Q000378:metabolism / Q000502:physiology*; D008247:Lysosomes / Q000201:enzymology / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism / Q000502:physiology; D050722:Oncogene Protein v-cbl; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex; D015682:Retroviridae Proteins, Oncogenic / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D025801:Ubiquitin / Q000378:metabolism* / Q000502:physiology; D044767:Ubiquitin-Protein Ligases; D019061:src-Family Kinases / Q000378:metabolism / Q000502:physiology*
D009097:Multienzyme Complexes; D050722:Oncogene Protein v-cbl; D015682:Retroviridae Proteins, Oncogenic; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; D019061:src-Family Kinases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D008025:Ligases