Jak3 is associated with CD40 and is critical for CD40 induction of gene expression in B cells

Jak3 is associated with CD40 and is critical for CD40 induction of gene expression in B cells
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DOI:
10.1016/s1074-7613(00)80281-2
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发表时间:
1997-04-01
期刊:
影响因子:
32.4
通讯作者:
Geha, RS
Geha, RS
中科院分区:
医学1区
文献类型:
--
作者:
Hanissian, SH;Geha, RS

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CD40是一种受体,对B淋巴细胞的生存、生长、分化和同型转换至关重要。虽然CD40缺乏固有的酪氨酸激酶活性,但它的连接诱导蛋白质酪氨酸磷酸化,这是CD40介导的一些事件所必需的。我们发现CD40的参与诱导JAK3和STAT3的酪氨酸磷酸化和激活。JAK3与CD40在结构上是相关的,这种相互作用需要在CD40的膜-近端区域有一个富含Pro的序列。该序列的缺失取消了CD40在8个细胞中诱导CD23、ICAM-1和淋巴毒素-α基因表达的能力。这些结果表明,通过JAK3的信号是由CD40激活的,并且在CD40介导的功能中起着重要作用。
CD40 is a receptor that is critical for the survival, growth, differentiation, and isotype switching of B lymphocytes. Although CD40 lacks intrinsic tyrosine kinase activity, its ligation induces protein tyrosine phosphorylation, which is necessary for several CD40-mediated events. We show that engagement of CD40 induces tyrosine phosphorylation and activation of Jak3 as well as of STAT3. Jak3 is constitutively associated with CD40, and this interaction requires a proline-rich sequence in the membrane-proximal region of CD40. Deletion of this sequence abolishes the capacity of CD40 to induce expression of CD23, ICAM-1, and lymphotoxin-alpha genes in 8 cells. These results indicate that signaling through Jak3 is activated by CD40 and plays an important role in CD40-mediated functions.