Action of novel non-receptor type protein-tyrosine kinase, p72^<syk>in immune cells.

新型非受体型蛋白酪氨酸激酶 p72^<syk> 在免疫细胞中的作用。

基本信息

批准号：
05670117
负责人：
YANAGI Shigeru
金额：
$ 1.41万
依托单位：
Fukui Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05670117/
关键词：
Syk protein-tyrosine kinase B cell Gene targeting Lyn Calcium mobilization platelets Translocation 抗Syk抗体インテグリン B細胞抗原レセプターコラーゲンレセプター PI3 kinase トランスローケーション p72syk インターロイキン2

项目摘要

We have reported a porcine gene sky encoding a non-receptor type 72-kDa PTK (p72^<syk>) which has a distinct structural character, that is the presence of the second src homology region 2 (SH2) instead of SH3, from other members of this group of PTK.Our efforts have in large part focused on the relationship between Syk in the context of surface receptor-initiated signal transduction in B cell and platelet because of their abundant localization.Stimulation of B lymphocytes through their antigen receptor (BCR) result in rapid increases and induces both an increase of phosphatidylinositol and mobilization of cytoplasmic free calcium. The BCR associates with two classes of tyrosine kinase : Src family kinase and Sky kinase. To dissect the functional roles of these two types of kinase in BCR signaling, Syk-deficient cell and Lyn-deficient cell lines were established. Syk-deficient cells abolished the tyrosine phosphorylation phospholipase C (PLC) -gamma, resulting in no inositol, 1,4,5-tris … More phosphate (IP3) generation, as well as calcium moblization upon receptor stimulation. Crosslinking of BCR on Lyn-deficient cells evoked a delayd and slow calcium moblization, despite the normal kinetics of IP3 turnover. These results demonstrated that Syk mediates IP3 generation, whereas Lyn regulates calcium mobization through a process independent of IP3 generation.Activation of Syk in platelets is not restricted to thrombin stimulation. Platelet activating factor, thromboxane A2, wheat germ agglutinin, and collagen also activate Syk. These findings imply that Syk may be one of the key molecules through which various receptor signaling acts. Tyrosine phosphorylation of p125^<FAK> is followed by Syk activation upon integrin receptor stimulation, suggesting that phosphorylation of p125^<FAK> may be mediated by Syk. Reinforcing this idea, the physical association of Syk family PTKs with Src family PTKs or FAK family protein is observed. Furthermore, stimulation of platelets by thrombin induces the rapid translocation of Syk from the cytosolic fraction to the membrane and cytoskeletal fraction. This recruitment of Syk to membrane and cytoskeletal fraction may contribute to the thrombininduced activation of Syk. Less

我们报道了一个编码非受体型72-kDa PTK（p72^<syk>）的猪基因天空，其具有独特的结构特征，即第二SRC同源区2（SH2）而不是SH3而不是SH3而不是SH3，而不是SH3，而不是这组PTK的其他努力。通过其抗原受体（BCR）刺激B淋巴细胞会导致迅速增加，并诱导磷脂酰肌醇的增加和动员细胞质游离钙。 BCR与两类的酪氨酸激酶：SRC家族激酶和Sky激酶相关联。为了剖定这两种类型的激酶在BCR信号传导中的功能作用，建立了SYK缺陷细胞和缺陷型细胞系。 Syk缺陷型细胞废除了酪氨酸磷酸化磷酸化磷脂酶C（PLC）-gamma，导致无肌醇，1,4,5-三个 - 更多的磷酸盐（IP3）产生，以及受体刺激上的钙成真。尽管IP3转换的正常动力学，但在Lyn缺陷型细胞上的BCR在Lyn缺陷型细胞上的交联仍引起了延迟和缓慢的成钙化。这些结果表明，Syk介导IP3的产生，而Lyn通过独立于IP3生成的过程调节钙暴力。Syk在血小板中的激活不限于凝血酶刺激。血小板激活因子，血栓烷A2，小麦胚芽凝集素和胶原蛋白也激活SYK。这些发现表明SYK可能是各种受体信号传导的关键分子之一。 p125^<fak>的酪氨酸磷酸化之后是整联蛋白受体刺激后的SYK激活，这表明p125^<fak>的磷酸化可能是由SYK介导的。观察到SYK家族PTK与SRC家族PTK或FAK家族蛋白的物理关联，从而加强了这一想法。此外，通过凝血酶对血小板的模拟诱导SYK从胞质分数迅速转移到膜和细胞骨架分数。将SYK募集到膜和细胞骨架分数可能有助于凝血酶诱导的SYK激活。较少的