The protein product of the c-cbl protooncogene is phosphorylated after B cell receptor stimulation and binds the SH3 domain of Bruton's tyrosine kinase
| Autor: | Ruth C. Lovering, Roland J. Levinsky, S. Hinshelwood, Christine Kinnon, Giles O. Cory, L. Maccarthy-Morrogh |
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| Rok vydání: | 1995 |
| Předmět: |
Ubiquitin-Protein Ligases
Molecular Sequence Data Immunology Receptors Antigen B-Cell macromolecular substances Protein tyrosine phosphatase SH2 domain SH3 domain Receptor tyrosine kinase Cell Line chemistry.chemical_compound immune system diseases Proto-Oncogene Proteins hemic and lymphatic diseases Agammaglobulinaemia Tyrosine Kinase Humans Immunology and Allergy Bruton's tyrosine kinase Proto-Oncogene Proteins c-cbl DNA Primers B-Lymphocytes Base Sequence biology Tyrosine phosphorylation Articles Protein-Tyrosine Kinases Phosphoproteins Molecular biology chemistry biology.protein GRB2 Tyrosine kinase Protein Binding Signal Transduction |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| DOI: | 10.1084/jem.182.2.611 |
| Popis: | X-linked agammaglobulinemia, a B cell immunodeficiency, is caused by mutations in the Bruton's tyrosine kinase (Btk) gene. The absence of a functional Btk protein leads to a failure of B cell differentiation and antibody production. B cell receptor stimulation leads to the phosphorylation of the Btk protein and it is, therefore, likely that Btk is involved in B cell receptor signaling. As a nonreceptor tyrosine kinase, Btk is likely to interact with several proteins within the context of a signal transduction pathway. To understand such interactions, we have generated glutathione S-transferase fusion proteins corresponding to different domains of the human Btk protein. We have identified a 120-kD protein present in human B cells as being bound by the SH3 domain of Btk and which, after B cell receptor stimulation, is one of the major substrates of tyrosine phosphorylation. We have shown that this 120-kD protein is the protein product of c-cbl, a protooncogene, which is known to be phosphorylated in response to T cell receptor stimulation and to interact with several other tyrosine kinases. Association of the SH3 domain of Btk with p120cbl provides evidence for an analogous role for p120cbl in B cell signaling pathways. The p120cbl protein is the first identified ligand of the Btk SH3 domain. |
| Databáze: | OpenAIRE |
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