STRADA(也称为STE20相关激酶适配蛋白α)属于AMPK相关激酶家族,是LKB1-STRAD-MO25复合体的关键组成部分。这个基因编码的蛋白质不具激酶活性,但作为支架蛋白与LKB1(一种肿瘤抑制激酶)和MO25结合,帮助LKB1定位到细胞质并激活其激酶功能。LKB1-STRAD-MO25复合体在细胞能量感应、极性建立和代谢调控中起核心作用,特别是通过磷酸化AMPK(AMP激活蛋白激酶)调控葡萄糖和脂质代谢。STRADA主要在肝脏、骨骼肌和大脑中表达,其功能异常与多种疾病相关。STRADA突变会导致PMSE综合征(伴癫痫的局灶性皮质发育不良),表现为智力障碍、癫痫和脑结构异常,这是因为突变破坏了LKB1的定位和功能,影响神经元迁移和极化。STRADA过表达可能增强LKB1活性,导致AMPK通路过度激活,可能改善胰岛素敏感性但抑制细胞生长;而表达降低会削弱LKB1功能,扰乱能量平衡,促进肿瘤发生。STRADA属于STRAD基因家族,包括STRADA和STRADB,两者结构相似(都含有假激酶结构域)且都能与LKB1结合,但组织分布和调控特性略有差异。该家族蛋白的共同特点是作为假激酶调节其他激酶活性,参与细胞信号转导和代谢调控。STRADA还通过LKB1影响mTOR、MARK等通路,间接调控细胞增殖、极性和代谢重编程。在癌症中,STRADA表达异常可能通过改变LKB1活性影响肿瘤进展,其表达水平在某些癌症中可能成为预后指标。此外,STRADA在神经发育中的作用使其成为神经退行性疾病的研究靶点。
The protein encoded by this gene contains a STE20-like kinase domain, but lacks several residues that are critical for catalytic activity, so it is termed a 'pseudokinase'. The protein forms a heterotrimeric complex with serine/threonine kinase 11 (STK11, also known as LKB1) and the scaffolding protein calcium binding protein 39 (CAB39, also known as MO25). The protein activates STK11 leading to the phosphorylation of both proteins and excluding STK11 from the nucleus. The protein is necessary for STK11-induced G1 cell cycle arrest. A mutation in this gene has been shown to result in polyhydramnios, megalencephaly, and symptomatic epilepsy (PMSE) syndrome. Multiple transcript variants encoding different isoforms have been found for this gene. Additional transcript variants have been described but their full-length nature is not known. [provided by RefSeq, Sep 2009]
由该基因编码的蛋白质包含一个STE20样激酶结构域,但缺少几个残基对于催化活性关键的,因此它被称为“假性‘。该蛋白与丝氨酸/苏氨酸激酶11(STK11,也称为LKB1)和支架蛋白钙结合蛋白39(CAB39,也称为MO25)一个异源复合物。该蛋白质激活STK11导致两种蛋白质的磷酸化和从细胞核排除STK11。该蛋白质是必需的STK11诱导G1期的细胞周期停滞。在这个基因的突变已显示导致羊水,巨脑,和症状性癫痫(PMSE)综合症。已发现该基因编码不同亚型的多个抄本变形。额外转录变体已被描述,但是它们的全长性质是未知的。 [由RefSeq的,2009年09月提供]
STRADA基因(以及对应的蛋白质)的细胞分布位置:
STRADA基因的本体(GO)信息:
名称 |
---|
4152 AMPK signaling pathway [PATH:hsa04152] |
4150 mTOR signaling pathway [PATH:hsa04150] |
名称 |
---|
Energy dependent regulation of mTOR by LKB1-AMPK |
IGF1R signaling cascade |
Insulin receptor signalling cascade |
IRS-mediated signalling |
IRS-related events |
IRS-related events triggered by IGF1R |
mTOR signalling |
PI3K Cascade |
PKB-mediated events |
Regulation of AMPK activity via LKB1 |
Signaling by Insulin receptor |
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) |
疾病名称 | 关系值 | NofPmids | NofSnps | 来源 |
Polyhydramnios, Megalencephaly, And Symptomatic Epilepsy | 0.24 | 0 | 0 | CLINVAR_CTD_human |
Medulloblastoma | 0.120271442 | 1 | 0 | BeFree_CTD_human |
Adenocarcinoma | 0.000271442 | 1 | 0 | BeFree |
Peutz-Jeghers Syndrome | 0.000271442 | 1 | 0 | BeFree |
Congenital Abnormality | 0.000271442 | 1 | 0 | BeFree |
Epilepsy | 0.000271442 | 1 | 0 | BeFree |
Myeloproliferative disease | 0.000271442 | 1 | 0 | BeFree |
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