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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
- Source :
- The Journal of Experimental Medicine
- Publication Year :
- 1995
- Publisher :
- Rockefeller University Press, 1995.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 15409538 and 00221007
- Volume :
- 182
- Database :
- OpenAIRE
- Journal :
- Journal of Experimental Medicine
- Accession number :
- edsair.doi.dedup.....0320ab7cc5a6b898407b8e00242bd8f6