Cbl-b (D3C12) Rabbit mAb

• 产品编号：CST-9498S      品牌：CST       原厂货号：9498S
• 产品分类：抗体 > 一抗 > 蛋白特异性一抗
• 应用分类：

描述：

Cbl-b (D3C12) Rabbit mAb兔单抗识别内源性的Cbl-b总蛋白。该抗体与c-Cbl并无交叉反应，并且基于序列比对预测其与Cbl-c也无交叉反应性。该单克隆抗体经合成与人Cbl-b蛋白羧基末端的邻近氨基酸残基序列一致的肽段，免疫动物产生。Cbl蛋白（在哺乳动物中为c-Cbl, Cbl-b, 和Cbl-c）是一个具有单亚基环指蛋白-泛素E3连接酶家族，其包含多种蛋白相互作用模序(1)。所有的Cbl蛋白具有高度保守的N-末端酪氨酸激酶结合(TKB)结构域，该结构域可以介导Cbl蛋白与磷酸化后Cbl底物酪氨酸残基之间的相互作用。环指的C-末端，Cbl蛋白具有富含脯氨酸的结构域，可介导与含有SH3结构域蛋白的相互作用。对酪氨酸残基的磷酸化可介导与含有SH2结构域的蛋白相互作用，诸如PI3K 的p85亚基。这些蛋白-蛋白相互作用模序，赋予了Cbl家族蛋白具有调节蛋白的功能(2)。通过对特殊底物的泛素化作用和分解作用，这一调节功能促成了Cbl 蛋白的E3-依赖活性。这一调节功能也促成了非-E3依赖活性，诸如受体酪氨酸激酶内化作用中对蛋白的募集作用、Cbl蛋白在特殊亚细胞组分的定位作用、以及离散的信号转导途径的激活作用(1)。Cbl-b是一种E3泛素连接酶，具有与c-Cbl几乎相同的结构域。Cbl-b在造血细胞生理学的作用已经被报道。Cbl-b的表达对于抗原识别过程中TCR表达的下调很重要(2)。Cbl-b通过对PI3K的调节亚基p85的泛素化(3,4)，实现CD28信号级联放大到Vav 和Rac1的负向调节作用。作为T淋巴细胞克隆无反应的一种重要的调节剂，Cbl-b mRNA和蛋白在钙动员和神经钙蛋白活化后，对T细胞进行增量调节(5)。Cbl-b缺乏的T细胞对无反应诱导有抵抗作用(5)。分子事件控制的这一表型被认为与PLCγ1和PKCθ泛素化作用有关，由于野生型无反应T细胞重新刺激后出现这些信号分子的降解，在Cbl-b缺乏的T细胞中并不出现(5)。

1. Schmidt, M.H. and Dikic, I. (2005) Nat Rev Mol Cell Biol 6, 907-18.
2. Naramura, M. et al. (2002) Nat Immunol 3, 1192-9.
3. Chiang, Y.J. et al. (2000) Nature 403, 216-20.
4. Fang, D. and Liu, Y.C. (2001) Nat Immunol 2, 870-5.
5. Heissmeyer, V. et al. (2004) Nat Immunol 5, 255-65.

原厂资料：

Homology

Species predicted to react based on 100% sequence homology: Bovine

Specificity / Sensitivity

Cbl-b (D3C12) Rabbit mAb recognizes endogenous levels of total Cbl-b protein. This antibody does not cross-react with c-Cbl and based upon sequence alignment, is not predicted to cross-react with Cbl-c.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to residues near the carboxy terminus of human Cbl-b protein.

Background

The Casitas B lineage lymphoma (Cbl) proteins (in mammals these are c-Cbl, Cbl-b, and Cbl-c) are a family of single subunit RING finger protein-ubiquitin E3 ligases that contain multiple protein interaction motifs (1). All Cbl proteins have a highly conserved N-terminal tyrosine kinase-binding (TKB) domain that mediates interactions between Cbl proteins and phosphorylated tyrosine residues on Cbl substrates. C-terminal to the RING finger, Cbl proteins have proline-rich domains that mediate interactions with SH3 domain-containing proteins. Phosphorylated tyrosine residues mediate interactions with SH2 domain-containing proteins such as the p85 subunit of PI3K. These protein-protein interaction motifs allow Cbl family proteins to function as adaptor proteins (2). This adaptor function contributes to the E3-dependent activities of Cbl proteins by targeting specific substrates for ubiquitination and degradation. The adaptor function also contributes to non-E3-dependent activities, such as the recruitment of proteins involved in receptor tyrosine kinase internalization, localization of Cbl proteins to specific subcellular compartments, and activation of discrete signaling pathways (1).Cbl-b is an E3 ubiquitin ligase with a domain organization nearly identical to that of c-Cbl. The role of Cbl-b in hematopoietic cell physiology is well documented. Cbl-b expression is important for the downregulation of TCR expression during antigen recognition (2). Cbl-b also acts as a potent negative regulator of the CD28 signaling cascade to Vav and Rac1 through its ability to ubiquitinate the p85 regulatory subunit of PI3K (3,4). As a critical regulator of clonal anergy in T lymphocytes, Cbl-b mRNA and protein are upregulated in T cells following calcium mobilization and calcineurin activation (5). Cbl-b-deficient T cells are resistant to anergy induction (5). The molecular events governing this phenotype are thought to be linked to defects in the ubiquitination of PLCγ1 and PKCθ since the degradation of these signaling molecules, which occurs following restimulation of wild-type anergic T cells, fails to occur in Cbl-b-deficient T cells (5).

1. Schmidt, M.H. and Dikic, I. (2005) Nat Rev Mol Cell Biol 6, 907-18.
2. Naramura, M. et al. (2002) Nat Immunol 3, 1192-9.
3. Chiang, Y.J. et al. (2000) Nature 403, 216-20.
4. Fang, D. and Liu, Y.C. (2001) Nat Immunol 2, 870-5.
5. Heissmeyer, V. et al. (2004) Nat Immunol 5, 255-65.

注意事项：

Storage: Supplied in 10 mM sodium HEPES (pH 7.5), 150
mM NaCl, 100 µg/ml BSA, 50% glycerol and less than 0.02%
sodium azide. Store at –20°C. Do not aliquot the antibody.