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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Dragone, Leonard L. Myers, Margaret D. Gadwal, Shyam Weiss, Arthur White, Carmen Sosinowski, Tomasz Gu, Hua |
| Description | Author Affiliation: Dragone LL ( Division of Pediatric Immunology/Rheumatology, Department of Pediatrics, University of California, San Francisco, CA 94143, USA.); |
| Abstract | Src-like adaptor protein (SLAP) and c-Cbl recently have been shown to cooperate in regulating T cell receptor (TCR) levels in developing T cells. SLAP also is expressed in developing B cells, and its deficiency leads to alterations in B cell receptor (BCR) levels and B cell development. Hence, we hypothesized that SLAP and c-Cbl may cooperate during B cell development to regulate BCR levels. In mice deficient in both SLAP and c-Cbl, we found that B cell development is altered, suggesting that they function through intersecting pathways. To study the mechanism by which SLAP and c-Cbl alter BCR levels, we coexpressed them in a mature mouse B cell line (Bal-17). First we determined that SLAP associates with proximal components of the BCR complex after stimulation and internalization. Coexpression of SLAP and c-Cbl in Bal-17 led to decreased surface and total BCR levels. This decrease in BCR levels depended on intact Src homology 2 (SH2) and C-terminal domains of SLAP. In addition, a mutation in the SH2 domain of SLAP blocked its colocalization with c-Cbl and the BCR complex, whereas deletion of the C terminus did not affect its localization. Last, coexpression of SLAP and c-Cbl altered BCR complex recycling. This alteration in BCR complex recycling depended on enzymatically active c-Cbl and Src family kinases, as well as the intact SH2 and C-terminal domains of SLAP. These data suggest that SLAP has a conserved function in B and T cells by adapting c-Cbl to the antigen-receptor complex and targeting it for degradation. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 48 |
| Volume Number | 103 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2006-11-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Proto-Oncogene Proteins C-cbl Metabolism Proto-Oncogene Proteins Pp60(c-src) Receptors, Antigen, B-Cell Animals B-Lymphocytes Cytology Immunology Cell Differentiation Cell Line, Tumor Down-Regulation Mice Mice, Inbred C57BL Mice, Knockout Protein Binding Deficiency Genetics Research Support, N.I.H., Extramural Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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