DUSP4(双特异性磷酸酶4)是一种属于双特异性磷酸酶(DUSP)家族的基因,该家族也称为MAPK磷酸酶(MKP),其主要功能是通过去磷酸化作用调控丝裂原活化蛋白激酶(MAPK)信号通路的活性。DUSP家族成员通常具有保守的催化结构域,能够特异性识别并去磷酸化MAPK家族成员(如ERK、JNK和p38)的酪氨酸和苏氨酸残基,从而负调控这些激酶的活性,影响细胞增殖、分化、凋亡和应激反应等关键生物学过程。DUSP4主要靶向ERK和JNK信号通路,在免疫调节、炎症反应和肿瘤发生中发挥重要作用。DUSP4的突变或表达异常可能导致MAPK信号通路的持续激活或抑制,进而影响细胞功能。例如,DUSP4的缺失或功能丧失突变可能导致ERK或JNK信号过度激活,促进炎症或肿瘤发展;而DUSP4的过表达则可能抑制MAPK通路,影响细胞生长和免疫应答。研究表明,DUSP4在多种癌症中表达异常,如乳腺癌、结肠癌和白血病,其表达水平可能与肿瘤的侵袭性和预后相关。此外,DUSP4还参与调节T细胞功能,影响自身免疫性疾病的发生。在炎症性疾病中,DUSP4通过调控巨噬细胞和树突细胞的活化,影响炎症因子的释放。DUSP4的过表达可能抑制免疫细胞的活化,降低炎症反应,但也可能导致免疫抑制;而DUSP4表达降低可能增强MAPK信号,促进炎症或自身免疫反应。DUSP4的功能还与其他DUSP家族成员存在冗余或协同作用,例如DUSP1和DUSP6也参与MAPK通路的调控,但各自对不同MAPK亚型的偏好性略有差异。总体而言,DUSP4是MAPK信号通路的重要负调控因子,其表达或功能异常与多种疾病密切相关,尤其在癌症和免疫相关疾病中具有潜在的治疗靶点价值。
The protein encoded by this gene is a member of the dual specificity protein phosphatase subfamily. These phosphatases inactivate their target kinases by dephosphorylating both the phosphoserine/threonine and phosphotyrosine residues. They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which are associated with cellular proliferation and differentiation. Different members of the family of dual specificity phosphatases show distinct substrate specificities for various MAP kinases, different tissue distribution and subcellular localization, and different modes of inducibility of their expression by extracellular stimuli. This gene product inactivates ERK1, ERK2 and JNK, is expressed in a variety of tissues, and is localized in the nucleus. Two alternatively spliced transcript variants, encoding distinct isoforms, have been observed for this gene. In addition, multiple polyadenylation sites have been reported. [provided by RefSeq, Jul 2008]
由该基因编码的蛋白是双重特异性蛋白磷酸酶亚家族的一个成员。这些通过磷酸酶脱磷酸化两个磷酸丝氨酸/苏氨酸和磷酸化酪氨酸残基的灭活他们的目标激酶。它们负调节有丝分裂原活化蛋白(MAP)激酶家族(MAPK / ERK,SAPK / JNK,p38的),其与细胞增殖和分化相关的成员。家庭双重特异性磷酸酶的不同成员显示各种MAP激酶,不同的组织分布和亚细胞定位,并通过细胞外刺激其表达诱导的不同模式不同的底物特异性。该基因产物灭活的ERK1,ERK2和JNK,在各种组织中表达,并且在细胞核中被定位。两种可变剪接转录物变体,编码不同同种型,已观察到该基因。此外,已经报道了多种多聚腺苷酸化位点。 [由RefSeq的,2008年7月提供]
DUSP4基因(以及对应的蛋白质)的细胞分布位置:
DUSP4基因的本体(GO)信息:
| 名称 |
|---|
| 4010 MAPK signaling pathway [PATH:hsa04010] |
| 名称 |
|---|
| Activated TLR4 signalling |
| ERK/MAPK targets |
| ERKs are inactivated |
| Immune System |
| Innate Immune System |
| MAP kinase activation in TLR cascade |
| MAPK targets/ Nuclear events mediated by MAP kinases |
| MyD88 cascade initiated on plasma membrane |
| MyD88 dependent cascade initiated on endosome |
| MyD88-independent TLR3/TLR4 cascade |
| MyD88:Mal cascade initiated on plasma membrane |
| NGF signalling via TRKA from the plasma membrane |
| Nuclear Events (kinase and transcription factor activation) |
| Signal Transduction |
| Signalling by NGF |
| Toll Like Receptor 10 (TLR10) Cascade |
| Toll Like Receptor 2 (TLR2) Cascade |
| Toll Like Receptor 3 (TLR3) Cascade |
| Toll Like Receptor 4 (TLR4) Cascade |
| Toll Like Receptor 5 (TLR5) Cascade |
| Toll Like Receptor 7/8 (TLR7/8) Cascade |
| Toll Like Receptor 9 (TLR9) Cascade |
| Toll Like Receptor TLR1:TLR2 Cascade |
| Toll Like Receptor TLR6:TLR2 Cascade |
| Toll-Like Receptors Cascades |
| TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation |
| TRAF6 Mediated Induction of proinflammatory cytokines |
| TRIF-mediated TLR3/TLR4 signaling |
| 疾病名称 | 关系值 | NofPmids | NofSnps | 来源 |
| Juvenile arthritis | 0.12 | 1 | 0 | CTD_human |
| Malignant neoplasm of breast | 0.001900093 | 7 | 0 | BeFree |
| Breast Carcinoma | 0.001628651 | 6 | 0 | BeFree |
| Colorectal Carcinoma | 0.000814326 | 3 | 0 | BeFree |
| Colorectal Cancer | 0.000814326 | 3 | 0 | BeFree |
| Malignant neoplasm of lung | 0.000542884 | 2 | 0 | BeFree |
| Carcinoma of lung | 0.000542884 | 2 | 0 | BeFree |
| Glioma | 0.000542884 | 2 | 1 | BeFree |
| Glioblastoma | 0.000271442 | 1 | 0 | BeFree |
| Cardiomyopathies | 0.000271442 | 1 | 0 | BeFree |
山东省济南市章丘区文博路2号 齐鲁师范学院 genelibs生信实验室
山东省济南市高新区舜华路750号大学科技园北区F座4单元2楼
电话: 0531-88819269
E-mail: product@genelibs.com
关注微信订阅号,实时查看信息,关注医学生物学动态。