Inagami T, Eguchi S, Numaguchi K, Motley E D, Tang H, Matsumoto T, Yamakawa T
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146, USA.
J Am Soc Nephrol. 1999 Jan;10 Suppl 11:S57-61.
In addition to its well known involvement in Gq/11-mediated vasoconstriction and its key roles in the homeostasis of electrolyte balances, the angiotensin II type 1 (AT1) receptor activates mitogen-activated protein kinase (MAPK) and p42/44 extracellular signal-regulated kinase. The extracellular signal-regulated kinase activation is mediated by activation of p21-Ras, Raf-1, and MAPK kinase in rat vascular smooth muscle cells. The mechanism for Gq-mediated activation of the tyrosine kinase pathways has not been clear. It was found that the initial release of intracellular Ca2+ results in the activation of the epidermal growth factor receptor (EGF-R), without autocrine release of epidermal growth factor. EGF-R provides a scaffold needed for the activation of p21-Ras, which leads to the activation of MAPK. MAPK plays pivotal roles in the activation of complex growth-promoting pathways. The pathway from the EGF-R involves protein tyrosine phosphorylation initiated by AT1 receptors. On the other hand, the angiotensin II type 2 (AT2) receptor counteracts the AT1 receptor-mediated tyrosine kinase activation by activating several tyrosine phosphatases and serine/threonine phosphatases, and it suppresses the cell growth process stimulated by various growth factors. The relative importance of AT1 and AT2 receptor actions depends on the levels of AT1 and AT2 receptor expression.
除了其在Gq/11介导的血管收缩中的广为人知的作用及其在电解质平衡稳态中的关键作用外，血管紧张素II 1型（AT1）受体还激活丝裂原活化蛋白激酶（MAPK）和p42/44细胞外信号调节激酶。在大鼠血管平滑肌细胞中，细胞外信号调节激酶的激活是由p21-Ras、Raf-1和MAPK激酶的激活介导的。Gq介导的酪氨酸激酶途径激活机制尚不清楚。研究发现，细胞内Ca2+的初始释放导致表皮生长因子受体（EGF-R）的激活，而无表皮生长因子的自分泌释放。EGF-R为p21-Ras的激活提供了所需的支架，进而导致MAPK的激活。MAPK在复杂的生长促进途径的激活中起关键作用。从EGF-R开始的途径涉及由AT1受体引发的蛋白质酪氨酸磷酸化。另一方面，血管紧张素II 2型（AT2）受体通过激活几种酪氨酸磷酸酶和丝氨酸/苏氨酸磷酸酶来抵消AT1受体介导的酪氨酸激酶激活，并抑制各种生长因子刺激的细胞生长过程。AT1和AT2受体作用的相对重要性取决于AT1和AT2受体的表达水平。
