The cbl oncogene: a novel substrate of protein tyrosine kinases.
The cbl oncogene was first identified as part of a transforming retrovirus which arose in a mouse pre-B cell lymphoma. Its protein product, p120cbl, is cytoplasmic and has several distinctive domains including a highly basic region, a RING finger motif and a large proline-rich domain. A mutation to cbl in the 70Z/3 pre-B cell lymphoma produces an oncogenic protein which exhibits a marked enhancement of tyrosine phosphorylation. Parallel studies have demonstrated that p120cbl is a substrate of protein Tyrosine kinases activated by engagement of the T cell antigen receptor and that cbl is phosphorylated by oncogenic forms of the Abl tyrosine kinase. These studies also demonstrated a constitutive association between cbl and the SHS domains of the Grb2 and Nck adaptor proteins in a range of haemopoietic cell lines. More recently it has been found that cbl is rapidly phosphorylated following stimulation of the EGF receptor, Fcy receptor, c-Kit receptor and CSF-1 receptor. A genetic analysis in Caenorhabditis elegans has identified a cbl homologue, called sli-1, that negatively regulates the LET-23 tyrosine kinase receptor. These characteristics indicate a central role for cbl in the regulation of intracellular signals that are mediated by growth factors and antigenic stimuli which activate protein tyrosine kinases.
Langdon
W Y
WY
Department of Biochemistry, University of Western Australia, Perth, WA.
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D006801:Humans; D051379:Mice; D008957:Models, Genetic; D009154:Mutation; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D050721:Proto-Oncogene Proteins c-cbl; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D044767:Ubiquitin-Protein Ligases
D011518:Proto-Oncogene Proteins; D011948:Receptors, Antigen, T-Cell; D050721:Proto-Oncogene Proteins c-cbl; D044767:Ubiquitin-Protein Ligases; D011505:Protein-Tyrosine Kinases; C067419:CBL protein, human; C493849:Cbl protein, mouse