SGK1 O00141

丝氨酸/苏氨酸蛋白激酶Sgk1 (EC 2.7.11.1) (血清/糖皮质激素调节激酶1)

功能描述

丝氨酸/苏氨酸蛋白激酶，参与调节多种离子通道、膜转运蛋白、细胞酶、转录因子、神经元兴奋性、细胞生长、增殖、存活、迁移和凋亡。在细胞应激反应中发挥重要作用。参与调节肾脏Na(+)潴留、肾脏K(+)排出、盐食欲、胃酸分泌、肠道Na(+)/H(+)交换和营养转运、胰岛素依赖性血压盐敏感性、外周葡萄糖摄取的盐敏感性、心脏复极化和记忆巩固。上调Na(+)通道：SCNN1A/ENAC、SCN5A和ASIC1/ACCN2，K(+)通道：KCNJ1/ROMK1、KCNA1-5、KCNQ1-5和KCNE1，上皮Ca(2+)通道：TRPV5和TRPV6，氯离子通道：BSND、CLCN2和CFTR，谷氨酸转运蛋白：SLC1A3/EAAT1、SLC1A2/EAAT2、SLC1A1/EAAT3、SLC1A6/EAAT4和SLC1A7/EAAT5，氨基酸转运蛋白：SLC1A5/ASCT2、SLC38A1/SN1和SLC6A19，肌酸转运蛋白：SLC6A8，Na(+)/二羧酸协同转运蛋白：SLC13A2/NADC1，Na(+)依赖性磷酸盐协同转运蛋白：SLC34A2/NAPI-2B，谷氨酸受体：GRIK2/GLUR6。上调载体：SLC9A3/NHE3、SLC12A1/NKCC2、SLC12A3/NCC、SLC5A3/SMIT、SLC2A1/GLUT1、SLC5A1/SGLT1和SLC15A2/PEPT2。调节酶：GSK3A/B、PMM2和Na(+)/K(+) ATPase，以及转录因子：CTNNB1和核因子NF-kappa-B。通过增强SCNN1A/ENAC的稳定性和表达来刺激钠离子转运进入上皮细胞。这是通过磷酸化NEDD4L泛素E3连接酶，促进其与14-3-3蛋白相互作用，从而阻止其与SCNN1A/ENAC结合并将其靶向降解来实现的。通过刺激ORAI1和STIM1调节钙库操纵性Ca(+2)内流(SOCE)。通过直接磷酸化KCNJ1/ROMK1或通过增强其与SLC9A3R2/NHERF2的相互作用间接调节KCNJ1/ROMK1。磷酸化MDM2并激活MDM2依赖性的p53/TP53泛素化。磷酸化MAPT/TAU并介导海马神经元中的微管解聚和神经突形成。磷酸化SLC2A4/GLUT4并上调其活性。磷酸化APBB1/FE65并促进其定位至细胞核。磷酸化MAPK1/ERK2并通过增强其与MAP2K1/MEK1和MAP2K2/MEK2的相互作用来激活它。磷酸化FBXW7并在NOTCH1信号传导中发挥抑制作用。磷酸化FOXO1导致其从细胞核重定位至细胞质。磷酸化FOXO3，促进其从细胞核移出并干扰FOXO3依赖性转录。磷酸化BRAF和MAP3K3/MEKK3并抑制其活性。响应地塞米松磷酸化SLC9A3/NHE3，导致其激活并增加其在细胞膜上的定位。磷酸化CREB1。血管生成过程中的血管重塑所必需的。持续的高水平和高活性可能导致高血压和糖尿病肾病等疾病。Isoform 2对SCNN1A/ENAC的细胞质膜表达和Na(+)转运的影响比isoform 1更大。 {ECO:0000269|PubMed:11154281, ECO:0000269|PubMed:11410590, ECO:0000269|PubMed:11696533, ECO:0000269|PubMed:12397388, ECO:0000269|PubMed:12590200, ECO:0000269|PubMed:12634932, ECO:0000269|PubMed:12650886, ECO:0000269|PubMed:12761204, ECO:0000269|PubMed:12911626, ECO:0000269|PubMed:14623317, ECO:0000269|PubMed:14706641, ECO:0000269|PubMed:15040001, ECO:0000269|PubMed:15044175, ECO:0000269|PubMed:15234985, ECO:0000269|PubMed:15319523, ECO:0000269|PubMed:15496163, ECO:0000269|PubMed:15733869, ECO:0000269|PubMed:15737648, ECO:0000269|PubMed:15845389, ECO:0000269|PubMed:15888551, ECO:0000269|PubMed:16036218, ECO:0000269|PubMed:16443776, ECO:0000269|PubMed:16982696, ECO:0000269|PubMed:17382906, ECO:0000269|PubMed:18005662, ECO:0000269|PubMed:18304449, ECO:0000269|PubMed:18753299, ECO:0000269|PubMed:19447520, ECO:0000269|PubMed:19756449, ECO:0000269|PubMed:20511718, ECO:0000269|PubMed:20730100, ECO:0000269|PubMed:21865597}.

组织特异性

Expressed in most tissues with highest levels in the pancreas, followed by placenta, kidney and lung. Isoform 2 is strongly expressed in brain and pancreas, weaker in heart, placenta, lung, liver and skeletal muscle.

亚细胞定位

Cytoplasm. Nucleus. Endoplasmic reticulum membrane. Cell membrane. Mitochondrion. Note=The subcellular localization is controlled by the cell cycle, as well as by exposure to specific hormones and environmental stress stimuli. In proliferating cells, it shuttles between the nucleus and cytoplasm in synchrony with the cell cycle, and in serum/growth factor-stimulated cells it resides in the nucleus. In contrast, after exposure to environmental stress or treatment with glucocorticoids, it is detected in the cytoplasm and with certain stress conditions is associated with the mitochondria. In osmoregulation through the epithelial sodium channel, it can be localized to the cytoplasmic surface of the cell membrane. Nuclear, upon phosphorylation.; SUBCELLULAR LOCATION: [Isoform 2]: Cell membrane.