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Interactions of Cbl with Grb2 and phosphatidylinositol 3'-kinase in activated Jurkat cells.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Meisner, H. M. Conway, Bruce R. Hartley, Danita |
| Copyright Year | 1995 |
| Abstract | T-cell receptor (TCR) cross-linking increases tyrosine phosphorylation of multiple proteins, only a few of which have been identified. One of the most rapidly tyrosine-phosphorylated polypeptides is the 120-kDa product of the proto-oncogene c-cbl, a cytosolic and cytoskeletal protein containing multiple proline-rich motifs that are potential binding sites for proteins containing Src homology 3 (SH3) domains. We report here that in cultured Jurkat T cells, Cbl is coprecipitated with antibody against the adapter protein Grb2. Upon activation of Jurkat T cells via the TCR-CD3 complex, we find that high-affinity binding of Cbl requires the N-terminal SH3 domain of GST-Grb2 fusion protein but after cross-linking of the TCR-CD3 and CD4 receptors, Cbl binds equally to its SH2 domain. Grb2 antisera also precipitated p85 from serum-starved cells, while TCR activation increased p85 and tyrosine-phosphorylated Cbl but not Cbl protein in Grb2 immunocomplexes. Phosphatidylinositol (PI) 3-kinase activity was immunoprecipitated from serum-starved cells with Cbl and to a lesser extent with Grb2 antisera, and TCR cross-linking increased this activity severalfold. The PI 3-kinase activity associated with Cbl amounted to 5 to 10% of the total cellular activity that could be precipitated by p85 antisera. The Ras exchange factor Son-of-sevenless 1 (Sos-1) was not found in anti-Cbl immunoprecipitates from activated cells, and Cbl was not detectable in anti-Sos-1 precipitates, supporting the likelihood that Sos-Grb2 and Cbl-Grb2 are present as distinct complexes. Taken together, these data suggest that Cbl function in Jurkat T cells involves its constitutive association with Grb2 and its recruitment of PI 3-kinase in response to TCR activation. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=2456&context=oapubs |
| PubMed reference number | 7791764v1 |
| Volume Number | 15 |
| Issue Number | 7 |
| Journal | Molecular and cellular biology |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Adaptor Proteins, Signal Transducing Affinity Binding Sites CBL gene CD3 Antigens CD4 Antigens Guanine Nucleotide Exchange Factors Homologous Gene Oncogenes Poly [ADP-Rbose] Polymerase 1 p85 Polypeptides Proline Protein Tyrosine Kinase Proto-Oncogenes Receptor-CD3 Complex, Antigen, T-Cell SH3 Domain T-Lymphocyte chimeric protein v-src protein |
| Content Type | Text |
| Resource Type | Article |
