Adapter protein BLNK
| Adapter protein BLNK | ||
|---|---|---|
| Properties of human protein | ||
| Mass / length primary structure | 50 kilodaltons / 456 amino acids (isoform 1)
48 kilodaltons / 433 amino acids (isoform 2) |
|
| Secondary to quaternary structure | Heterodimer | |
| Isoforms | 2 | |
| Identifier | ||
| Gene names | BLNK ; BASH; SLP65 | |
| External IDs | ||
| Occurrence | ||
| Parent taxon | Vertebrates | |
| Orthologue | ||
| human | House mouse | |
| Entrez | 29760 | 17060 |
| Ensemble | ENSG00000095585 | ENSMUSG00000061132 |
| UniProt | Q8WV28 | Q9QUN3 |
| Refseq (mRNA) | NM_001114094 | NM_008528 |
| Refseq (protein) | NP_001107566 | NP_032554 |
| Gene locus | Chr 10: 96.19 - 96.27 Mb | Chr 19: 40.93 - 40.99 Mb |
| PubMed search | 29760 |
17060
|
The adapter protein BLNK ( B cell l i nk he protein , and SLP-65 or BASH) is a protein that in B cells of vertebrates is expressed, and there is involved in the signal line of the B-cell receptor. Mutations in the human BLNK - gene are a rare form of agammaglobulinemia responsible.
BLNK is associated with the B-cell receptor and, after stimulation of this receptor, ensures the generation of a complex from different signal proteins. These include Bruton's tyrosine kinase and phospholipase C -gamma. BLNK has an atomic mass of 65 kDa and consists of an N-terminal region with five tyrosines , a central region with several binding proteins for SH3 domains and an SH2 domain at the C-terminus.
In cell lines it could be shown that BLNK is responsible for the activation of the phospholipase-C-gamma, and thus for the generation of a calcium signal (increase in the calcium ion concentration in the cell) after stimulation of the B-cell receptor. BLNK itself is phosphorylated by the kinase Syk and thus activated. Syk itself binds to the B-cell receptor activated by antigen binding and thus integrates BLNK in the B-cell receptor signaling pathway.
Knockout mice lacking BLNK show defective B-cell development. The number of mature B cells is markedly reduced in these mice. Most B-cell precursors do not get beyond the pre-B-cell stage. At this stage a preform of the B cell receptor is expressed for the first time. Another block in B-cell development occurs in immature B-cells. The BLNK-deficient B cells show, analogous to experiments with cell lines, a reduced calcium ion signal.
With SLP-76, T cells express a similar protein, which is not, however, functionally completely analogous. SLP-76 knockout mice show approximately one complete block in T cell development.
Individual evidence
- ↑ Orthologist at orthoDB
- ↑ orphanet: agammaglobulinaemia, autosomal recessive
- ↑ Jürgen Wienands, Jutta Schweikert, Bernd Wollscheid, Hassan Jumaa, Peter J. Nielsen, Michael Reth: SLP-65: A New Signaling Component in B Lymphocytes which Requires Expression of the Antigen Receptor for Phosphorylation. In: Journal of Experimental Medicine . vol. 188 no. 4, 1998, pp. 791-795. (on-line)
- ↑ Chong Fu1, Christoph W. Turck, Tomohiro Kurosaki, Andrew C. Chan: BLNK: a Central LinkerProtein in B Cell Activation. In: Immunity . Volume 9, Issue 1, 1998, pp. 93-103 (online)
- ↑ R. Goitsuka, Y. Fujimura, H. Mamada, A. Umeda, T. Morimura, K. Uetsuka, K. Doi, S. Tsuji, D. Kitamura: BASH, a novel signaling molecule preferentially expressed in B cells of the bursa of Fabricius. In: J. Immunol. 161, 1998, pp. 5804-5808 (online)
- ↑ Masamichi Ishiai, Mari Kurosaki, Rajita Pappu, Katsuya Okawa, Irina Ronko, Chong Fu, Masao Shibata, Akihiro Iwamatsu, Andrew C Chan, Tomohiro Kurosaki: BLNK Required for Coupling Syk to PLCγ2 and Rac1-JNK in B Cells. In: Immunity. Volume 10, Issue 1, 1999, pp. 117–125 (online)
- ↑ Janeway's immunobiology , 8th. Edition, Garland Science, 2011, ISBN 0815342438 , pp. 258-260.
- ↑ H. Jumaa, B. Wollscheid, M. Mitterer, J. Wienands, M. Reth, PJ Nielsen: Abnormal development and function of B lymphocytes in mice deficient for the signaling adapter protein SLP-65. In: Immunity. 11 (5), 1999, pp. 547-554. (on-line)
- ↑ JL Clements, B. Yang, SE Ross-Barta, SL Eliason, RF Hrstka, RA Williamson, GA Koretzky: Requirement for the leukocyte-specific adapter protein SLP-76 for normal T cell development. In: Science. 281, 1998, pp. 416-419 (online)