PHLPP1 O60346

PH域富含亮氨酸重复序列蛋白磷酸酶1 (EC 3.1.3.16) (Pleckstrin同源域包含家族E成员1) (含PH域家族E成员1) (视交叉上核昼夜节律振荡蛋白) (hSCOP)

功能描述

参与调节Akt和PKC信号传导的蛋白磷酸酶。介导AGC Ser/Thr蛋白激酶家族成员C末端结构域疏水基序的去磷酸化；特异性作用于AKT2和AKT3的'Ser-473'，PRKCB的'Ser-660'和PRKCA的'Ser-657' (PubMed:15808505, PubMed:17386267, PubMed:18162466)。Isoform 2似乎在调节海马神经元中的Akt信号传导中起主要作用 (By similarity)。Akt通过主要改变调节促凋亡和抗凋亡基因的转录因子功能的级联反应，调节细胞存活与凋亡之间的平衡。Akt的'Ser-473'去磷酸化触发凋亡并抑制肿瘤生长。PRKCA和PRKCB的去磷酸化导致其不稳定和降解 (PubMed:18162466)。使STK4在'Thr-387'去磷酸化，导致STK4激活和凋亡 (PubMed:20513427)。使RPS6KB1去磷酸化并参与帽依赖性翻译的调节 (PubMed:21986499)。抑制癌细胞增殖，可能作为肿瘤抑制因子 (PubMed:19079341)。使RAF1去磷酸化从而抑制其激酶活性 (PubMed:24530606)。可能作为膜筏中K-Ras信号传导的负调节因子 (By similarity)。参与海马依赖性的长期记忆形成 (By similarity)。通过调节重置后昼夜节律周期的巩固参与昼夜节律控制 (By similarity)。参与调节性T细胞的发育和功能 (By similarity)。 {ECO:0000250|UniProtKB:Q8CHE4, ECO:0000250|UniProtKB:Q9WTR8, ECO:0000269|PubMed:15808505, ECO:0000269|PubMed:17386267, ECO:0000269|PubMed:18162466, ECO:0000269|PubMed:19079341, ECO:0000269|PubMed:21986499, ECO:0000269|PubMed:24530606}.

组织特异性

In colorectal cancer tissue, expression is highest in the surface epithelium of normal colonic mucosa adjacent to the cancer tissue but is largely excluded from the crypt bases. Expression is lost or significantly decreased in 78% of tested tumors (at protein level). Ubiquitously expressed in non-cancerous tissues.

亚细胞定位

Cytoplasm. Membrane; Peripheral membrane protein. Nucleus. Note=In colorectal cancer tissue, expression is concentrated at the lateral membrane of epithelial cells.; SUBCELLULAR LOCATION: [Isoform 2]: Cell membrane