PDPK1 O15530

3-磷酸肌醇依赖性蛋白激酶1 (hPDK1) (EC 2.7.11.1)

功能描述

丝氨酸/苏氨酸激酶，作为主激酶，磷酸化并激活AGC蛋白激酶家族的一个亚群 (PubMed:10226025, PubMed:10480933, PubMed:10995762, PubMed:12167717, PubMed:14585963, PubMed:14604990, PubMed:16207722, PubMed:16251192, PubMed:17327236, PubMed:17371830, PubMed:18835241, PubMed:9094314, PubMed:9368760, PubMed:9445476, PubMed:9445477, PubMed:9707564, PubMed:9768361)。其靶标包括：蛋白激酶B (PKB/AKT1, PKB/AKT2, PKB/AKT3)，p70核糖体蛋白S6激酶 (RPS6KB1)，p90核糖体蛋白S6激酶 (RPS6KA1, RPS6KA2 和 RPS6KA3)，环AMP依赖性蛋白激酶 (PRKACA)，蛋白激酶C (PRKCD 和 PRKCZ)，血清和糖皮质激素诱导激酶 (SGK1, SGK2 和 SGK3)，p21激活激酶-1 (PAK1)，TSSK3，蛋白激酶PKN (PKN1 和 PKN2) (PubMed:10226025, PubMed:10480933, PubMed:10995762, PubMed:12167717, PubMed:14585963, PubMed:14604990, PubMed:16207722, PubMed:16251192, PubMed:17327236, PubMed:17371830, PubMed:18835241, PubMed:9094314, PubMed:9368760, PubMed:9445476, PubMed:9707564, PubMed:9768361)。在胰岛素信号转导中发挥核心作用，通过为PKB/AKT1提供激活磷酸化，从而将信号传播至控制细胞增殖和存活以及葡萄糖和氨基酸摄取和储存的下游靶标 (PubMed:10226025, PubMed:12167717, PubMed:9094314)。通过以下方式负向调节TGF-beta诱导的信号传导：调节SMAD3和SMAD7与TGF-beta受体的结合，磷酸化SMAD2、SMAD3、SMAD4和SMAD7，阻止SMAD3和SMAD4的核转位以及SMAD7在响应TGF-beta时从细胞核到细胞质的转位 (PubMed:17327236)。激活PPARG转录活性并促进脂肪细胞分化 (By similarity)。通过磷酸化IKKB激活NF-kappa-B通路 (PubMed:16207722)。酪氨酸磷酸化形式对于血管紧张素II调节粘着斑至关重要 (PubMed:14585963)。控制发育中胰腺细胞的增殖、存活和生长 (By similarity)。参与肥大细胞Ca(2+)内流和Ca(2+)激活的K(+)通道的调节 (By similarity)。对血管内皮细胞 (ECs) 的运动性至关重要，并参与其趋化性的调节 (PubMed:17371830)。通过作为细胞存活和β-肾上腺素能反应的双重效应因子，在心脏稳态中发挥关键作用 (By similarity)。通过调节前T细胞表面关键营养受体的表达并介导Notch诱导的细胞生长和增殖反应，在胸腺细胞发育过程中发挥重要作用 (By similarity)。为巨噬细胞中toll样受体介导的NF-kappa-B激活提供负反馈抑制 (By similarity)。 {ECO:0000250|UniProtKB:Q9Z2A0, ECO:0000269|PubMed:10226025, ECO:0000269|PubMed:10480933, ECO:0000269|PubMed:10995762, ECO:0000269|PubMed:12167717, ECO:0000269|PubMed:14585963, ECO:0000269|PubMed:14604990, ECO:0000269|PubMed:16207722, ECO:0000269|PubMed:16251192, ECO:0000269|PubMed:17327236, ECO:0000269|PubMed:17371830, ECO:0000269|PubMed:18835241, ECO:0000269|PubMed:9094314, ECO:0000269|PubMed:9368760, ECO:0000269|PubMed:9445476, ECO:0000269|PubMed:9445477, ECO:0000269|PubMed:9707564, ECO:0000269|PubMed:9768361}.; FUNCTION: [Isoform 3]: 无催化活性。 {ECO:0000269|PubMed:9445477}.

组织特异性

Appears to be expressed ubiquitously. The Tyr-9 phosphorylated form is markedly increased in diseased tissue compared with normal tissue from lung, liver, colon and breast.

亚细胞定位

Cytoplasm. Nucleus. Cell membrane; Peripheral membrane protein. Cell junction, focal adhesion. Note=Tyrosine phosphorylation seems to occur only at the cell membrane. Translocates to the cell membrane following insulin stimulation by a mechanism that involves binding to GRB14 and INSR. SRC and HSP90 promote its localization to the cell membrane. Its nuclear localization is dependent on its association with PTPN6 and its phosphorylation at Ser-396. Restricted to the nucleus in neuronal cells while in non-neuronal cells it is found in the cytoplasm. The Ser-241 phosphorylated form is distributed along the perinuclear region in neuronal cells while in non-neuronal cells it is found in both the nucleus and the cytoplasm. IGF1 transiently increases phosphorylation at Ser-241 of neuronal PDPK1, resulting in its translocation to other cellular compartments. The tyrosine-phosphorylated form colocalizes with PTK2B in focal adhesions after angiotensin II stimulation.