RHO GTPases 激活 PKNs
中文名称
通路描述
蛋白激酶 N（PKN），也称为蛋白激酶 C 相关激酶（PKR），具有 C 端丝氨酸/苏氨酸激酶结构域和 N 端三个 RHO 结合基序。RHO GTPase（RHOA、RHOB、RHOC 和 RAC1）与 PKN1、PKN2 和 PKN3 结合，将其与 PIP3 激活的共激活因子 PDPK1（PDK1）拉近。PDPK1 在激酶激活环上高度保守的丝氨酸残基上磷酸化 PKNs，这是 PKN 激活的前提条件。其他残基的磷酸化也可能参与激活（Flynn et al. 2000, Torbett et al. 2003, Dettori et al. 2009）。PKNs 在体外可由脂肪酸如花生四烯酸和磷脂激活，但其体内意义尚不清楚（Palmer et al. 1995, Yoshinaga et al. 1999）。PKNs 在多种功能中发挥重要作用，包括细胞周期调节、受体转运、囊泡运输和凋亡。PKN 还参与受体和配体依赖的雄激素受体转录激活。已证明超过 20 种蛋白质和几种肽段被 PKN1 和 PKN2 磷酸化，包括 CPI-17（Hamaguchi et al. 2000）、α-肌动蛋白（Mukai et al. 1997）、adducin（Collazos et al. 2011）、CDC25C（Misaki et al. 2001）、肌动蛋白（Matsuzawa et al. 1997）、TRAF1（Kato et al. 2008）、CLIP170（Collazos et al. 2011）和 EGFR（Collazos et al. 2011）。目前已知 PKN3 没有已知的底物（Collazos et al. 2011）。
英文描述
Glucagon signaling in metabolic regulation Glucagon and insulin are peptide hormones released from the pancreas into the blood, that normally act in complementary fashion to stabilize blood glucose concentration. When blood glucose levels rise, insulin release stimulates glucose uptake from the blood, glucose breakdown (glycolysis), and glucose storage as glycogen. When blood glucose levels fall, glucagon release stimulates glycogen breakdown and de novo glucose synthesis (gluconeogenesis), while inhibiting glycolysis and glycogen synthesis.
At a molecular level, the binding of glucagon to the extracellular face of its receptor causes conformational changes in the receptor that allow the dissociation and activation of subunits Gs and Gq. The activation of Gq leads to the activation of phospholipase C, production of inositol 1,4,5-triphosphate, and subsequent release of intracellular calcium. The activation of Gs leads to activation of adenylate cyclase, an increase in intracellular cAMP levels, and activation of protein kinase A (PKA). Active PKA phosphorylates key enzymes of glycogenolysis, glycogenesis, gluconeogenesis, and glycolysis, modifying their activities. These signal transduction events, and some of their downstream consequences, are illustrated below (adapted from Jiang and Zhang, 2003).
At a molecular level, the binding of glucagon to the extracellular face of its receptor causes conformational changes in the receptor that allow the dissociation and activation of subunits Gs and Gq. The activation of Gq leads to the activation of phospholipase C, production of inositol 1,4,5-triphosphate, and subsequent release of intracellular calcium. The activation of Gs leads to activation of adenylate cyclase, an increase in intracellular cAMP levels, and activation of protein kinase A (PKA). Active PKA phosphorylates key enzymes of glycogenolysis, glycogenesis, gluconeogenesis, and glycolysis, modifying their activities. These signal transduction events, and some of their downstream consequences, are illustrated below (adapted from Jiang and Zhang, 2003).
所含基因
27 个基因