TYROSINE PHOSPHORYLATION AND ACTIVATION OF BRUTON TYROSINE KINASE UPON FC-EPSILON-RI CROSS-LINKING
TYROSINE PHOSPHORYLATION AND ACTIVATION OF BRUTON TYROSINE KINASE UPON FC-EPSILON-RI CROSS-LINKING
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DOI：
10.1128/mcb.14.8.5108
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发表时间：
1994-08-01
影响因子：
5.3
通讯作者：
KAWAKAMI, T
中科院分区：
文献类型：
--
作者：
KAWAKAMI, Y;YAO, LB;KAWAKAMI, T
几种细胞蛋白的酪氨酸磷酸化是肥大细胞或嗜碱性细胞上免疫球蛋白E高亲和受体（Fc epsilon RI）交联诱导的最早信号事件之一。在此过程中激活的酪氨酸激酶包括Src家族的Lyn、c-Yes和c-Src，以及另一个亚家族的成员Syk和PTK72（与Syk相同或高度相关）。最近，我们中的一些人描述了两种新的酪氨酸激酶，Emb和Emt，它们的表达仅限于造血细胞亚群，包括肥大细胞。Emb被证明与Btk相同，Btk是人类x连锁无球蛋白血症和x连锁免疫缺陷小鼠中存在缺陷的基因产物。在这里，我们报道了Fc epsilon RI交联诱导小鼠骨髓源肥大细胞中酪氨酸、丝氨酸和苏氨酸残基的快速磷酸化和Btk的激活。受体交联后，一小部分Btk从细胞质转移到膜室。Ca2+离子载体（A23187）、12-肉豆酸酯13-醋酸酯或这两种试剂的组合都不能诱导酪氨酸磷酸化。未检测到Btk与受体亚基β或γ之间的共免疫沉淀。这些数据共同表明，Btk与Fc epsilon RI无关，但其激活发生在蛋白激酶C激活之前，并在Fc epsilon RI信号通路中起着新的作用。
Tyrosine phosphorylation of several cellular proteins is one of the earliest signaling events induced by cross-linking of the high-affinity receptor for immunoglobulin E (Fc epsilon RI) on mast cells or basophils. Tyrosine kinases activated during this process include the Src family kinases, Lyn, c-Yes, and c-Src, and members of another subfamily, Syk and PTK72 (identical or highly related to Syk). Recently, some of us described two novel tyrosine kinases, Emb and Emt, whose expression was limited to subsets of hematopoietic cells, including mast cells. Emb turned out to be identical to Btk, a gene product defective in human X-linked agammaglobulinemia and in X-linked immunodeficient (rid) mice. Here we report that Fc epsilon RI cross-linking induced rapid phosphorylation on tyrosine, serine, and threonine residues and activation of Btk in mouse bone marrow-derived mast cells. A small fraction of Btk translocated from the cytosol to the membrane compartment following receptor cross-linking. Tyrosine phosphorylation df Btk was not induced by either a Ca2+ ionophore (A23187), phorbol 12-myristate 13-acetate, or a combination of the two reagents. Coimmunoprecipitation between Btk and receptor subunit beta or gamma was not detected. The data collectively suggest that Btk is not associated with Fc epsilon RI but that its activation takes place prior to protein kinase C activation and plays a novel role in the Fc epsilon RI signaling pathway.