RENIN/ANGIOTENSIN SYSTEM AND INJURY

血管紧张素II可以作为生长和分化因子， 平滑肌和肾细胞。 虽然生物化学的 血管紧张素II的传统作用被详细地理解， 血管紧张素II的生化作用导致生长调节， 就不那么清楚了 这项资助采用了一种假设，即为了理解 血管紧张素II介导的细胞生长和分化， 研究当血管紧张素II 与AT 1受体结合。 一种这样的途径是Jak激酶， STAT转录因子。 我的团队已经做了一个重要的 在描述AT 1激活这一途径的贡献 受体的 我们建议继续这些研究， At 1受体与Jak 2激酶（特异性Aim 1）和 Stat 1（具体目标2）。 我们假设AT 1的一个关键区域 受体是在羧基末端尾中发现的信号基序YIPP 受体，而这个基序是必要的血管紧张素II- 介导的Jak-STAT激活。 具体目标3是调查 YIPP基序在非STAT信号传导中的作用。 的最后部分 该基金将用于研究Jak-STAT通路在血管紧张素II 依赖细胞增殖。

Angiotensin II can act as a growth and differentiation factor for both smooth muscle and renal cells. While the biochemistry of the traditional effects of angiotensin II are understood in some detail, the biochemical actions of angiotensin II leading to growth regulation are far less clear. This grant adopts the hypothesis that to understand angiotensin II-mediated cell growth and differentiation, it is critical to study the intracellular signaling events initiated when angiotensin II binds to the AT 1 receptor. One such pathway is the Jak kinases and STAT transcription factors. My group has made an important contribution in describing the activation of this pathway by the AT 1 receptor. We propose to continue these studies by dissecting the binding of the At1 receptor with Jak2 kinase (Specific Aim 1) and with Stat1 (Specific Aim 2). We postulate that a critical region of the AT1 receptor is the signaling motif YIPP found in the carboxy terminal tail of the receptor, and that t his motif is necessary for angiotensin II- mediated Jak-STAT activation. Specific Aim 3 is to investigate the role of the YIPP motif in non-STAT signaling. The final portion of the grant is to study the role of the Jak-STATpathway in angiotensin II dependent cell proliferation.