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.
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.
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DOI：
10.1084/jem.182.2.611
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发表时间：
1995-08-01
影响因子：
15.3
通讯作者：
Kinnon, Christine
中科院分区：
文献类型：
--
作者：
Cory, Giles O. C.;Lovering, Ruth C.;Hinshelwood, Steve;Maccarthy-Morrogh, Lucy;Levinsky, Roland J.;Kinnon, Christine
X 连锁无丙种球蛋白血症是一种 B 细胞免疫缺陷，由布鲁顿酪氨酸激酶 (Btk) 基因突变引起。功能性 Btk 蛋白的缺失会导致 B 细胞分化和抗体产生失败。 B 细胞受体刺激会导致 Btk 蛋白磷酸化，因此 Btk 很可能参与 B 细胞受体信号转导。作为一种非受体酪氨酸激酶，Btk 可能在信号转导途径中与多种蛋白质相互作用。为了理解这种相互作用，我们生成了与人类 Btk 蛋白不同结构域相对应的谷胱甘肽 S-转移酶融合蛋白。我们已经鉴定出人类 B 细胞中存在的一种 120 kD 蛋白质与 Btk 的 SH3 结构域结合，在 B 细胞受体刺激后，该蛋白质是酪氨酸磷酸化的主要底物之一。我们已经证明，这种 120 kD 的蛋白质是 c-cbl 的蛋白质产物，c-cbl 是一种原癌基因，已知它会响应 T 细胞受体刺激而被磷酸化，并与其他几种酪氨酸激酶相互作用。 Btk 的 SH3 结构域与 p120cbl 的关联为 p120cbl 在 B 细胞信号传导通路中发挥类似作用提供了证据。 p120cbl 蛋白是第一个被识别的 Btk SH3 结构域配体。
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.
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影响因子：
64.8
作者：
LIM, WA;RICHARDS, FM;FOX, RO
通讯作者：
FOX, RO
影响因子：
3.5
作者：
BRADLEY, LAD;SWEATMAN, AK;KINNON, C
通讯作者：
KINNON, C
影响因子：
5.3
作者：
BURKHARDT, AL;COSTA, T;NUSSENZWEIG, MC
通讯作者：
NUSSENZWEIG, MC
影响因子：
5.4
作者：
GENEVIER, HC;HINSHELWOOD, S;LOVERING, RC
通讯作者：
LOVERING, RC
影响因子：
56.9
作者：
REN, RB;MAYER, BJ;BALTIMORE, D
通讯作者：
BALTIMORE, D