Signaling through surface receptors in immune cells.

通过免疫细胞表面受体发出信号。

基本信息

批准号：
09044263
负责人：
TAKATSU Kiyoshi
金额：
$ 3.46万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for international Scientific Research
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09044263/
关键词：
IL-5 B cell differentiation Cytokine Cell adhesion Tyrosine kinase Btk JAK2 STAT5 PI 3-kinase チロシンキナーゼアダプター分子 B細胞シグナル伝達 IL-5

项目摘要

The human IL-5R (hIL-5R) consists of two distinct polypeptide chains, alpha and beta which activates JAK1 and JAK2 and STAT5. We analyzed the interaction between hIL-5Ralpha and betac by immuno-precipitation using anti-hIL-5Ralpha and anti-betac mAbs. The binding of JAK1 and JAK2 to each hIL-5R subunit was also evaluated inTF-h5Ralpha. IL-5 stimulation induced the recruitment of betac to hIL-5Ralpha, although in the absence of IL-5 the subunits remained independent. JAK2 and JAK1 were associated with hIL-5Ralpha and betac, respectively. IL-S stimulation resulted in tyrosine phosphoryl-ation of JAK2, JAK1, betac, and STAT5. Moreover, IL-5-induced dimerization of IL-5R subunits caused JAK2 activation and the betac phosphorylation. Furthermore, tyrosine phosphorylation of JAK1 depended on the activation of JAK2. The cytoplasmic stretch at position 346-387, containing the proline-rich region was necessary for JAK2 binding. These observations suggest that activation of hIL-5Ralpha associated JAK2 is indispensable for IL-5 signaling event.Bone-marrow derived mast cells adhered to fibronectin via VLA-5 (alpha5beta1) upon stimulation with steel factor (SLF) and FceRI cross-linking as well as PMA.SLF and PMA, but not FcepsilonRI cross-linking induced a diffusion of VLA-5 as well as drastic morphological changes. In contrast, only FcepsilonRI cross-linking increased affinity of VLA-5. We also showed PI 3-kinase as a critical affinity modulator by a specific inhibitor, wortmannin, and by introduction ofa constitutively active p110 subunit ofPI-3 kinase. Utilization of affinity or spatial modulation of VLA-5 caused differential effects on adhesion in the presence of physiological concentrations of soluble fibronectin. Our findings indicate that adhesion via VLA-5 are regulated physiologically by two mechanisms ; affinity modulation through PI 3-kinase and spatial modulation possibly through protein kinase C.

人IL-5R（HIL-5R）由两个不同的多肽链组成，即α和β，它们激活JAK1和JAK2和STAT5。我们使用抗HIL-5ralpha和抗βMABS分析了HIL-5RALPHA和BETAC之间的相互作用。还评估了JAK1和JAK2与每个HIL-5R亚基的结合Intf-H5ralpha。 IL-5刺激诱导了BETAC募集到HIL-5ralpha，尽管在没有IL-5的情况下，亚基仍然独立。 JAK2和JAK1分别与Hil-5ralpha和Betac相关。 IL-S刺激导致JAK2，JAK1，BETAC和STAT5的酪氨酸磷酸化。此外，IL-5诱导的IL-5R亚基二聚化导致JAK2激活和BETAC磷酸化。此外，JAK1的酪氨酸磷酸化取决于JAK2的激活。在346-387位的胞质拉伸，包含富含脯氨酸的区域的JAK2结合是必需的。这些观察结果表明，与IL-5信号事件相关的HIL-5RALPHA相关的JAK2的激活是必不可少的。在用VLA-5（Alpha5beta1）用钢因子（SLF）（SLF）和FCERI交叉链接的bbon-Marow通过VLA-5（Alpha5beta1）粘附在纤连蛋白上的boRON-MART以及PMA.SLF和PMANRINK和PMANRINK和PMAINNINK，但也是如此。 VLA-5的扩散以及急剧的形态变化。相反，只有fcepsilonri交联增加了VLA-5的亲和力。我们还通过特定的抑制剂wortmannin和Pi-3激酶的组成型p110亚基来展示PI 3-激酶作为临界亲和力调节剂。在存在生理浓度的可溶性纤连蛋白的情况下，利用亲和力或VLA-5的空间调节对粘附产生了不同的影响。我们的发现表明，通过VLA-5的粘附受到了两种机制的生理调节。通过PI 3-激酶和空间调节的亲和力调节可能通过蛋白激酶C进行。