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  4. LRRK2 Recombinant Monoclonal Antibody

LRRK2 Recombinant Monoclonal Antibody

  • 中文名稱：
    LRRK2重組抗體
  • 貨號：
    CSB-RA797150A0HU
  • 規(guī)格：
    ￥1320
  • 圖片：
    • IHC image of CSB-RA797150A0HU diluted at 1:100 and staining in paraffin-embedded human kidney tissue performed on a Leica BondTM system. After dewaxing and hydration, antigen retrieval was mediated by high pressure in a citrate buffer (pH 6.0). Section was blocked with 10% normal goat serum 30min at RT. Then primary antibody (1% BSA) was incubated at 4℃ overnight. The primary is detected by a Goat anti-rabbit IgG polymer labeled by HRP and visualized using 0.05% DAB.
  • 其他：

產(chǎn)品詳情

  • 產(chǎn)品描述：

    LRRK2 belongs to the ROCO protein family and is a large multidomain protein. In cells, LRRK2 phosphorylates a set of Rab GTPases, which is accelerated by Parkinson's disease-related LRRK2 mutations. Evidence has shown that LRRK2 governs intracellular vesicle trafficking and organelle maintenance, including Golgi, endosomes, and lysosomes. LRRK2 gene mutations are a common genetic risk factor for both familial and sporadic Parkinson's disease (PD). LRRK2 kinase activity has been demonstrated to be altered by its pathogenic mutations, and aberrant increases in LRRK2 kinase activity are thought to contribute to PD pathogenesis.

    CUSABIO cloned LRRK2 antibody-coding genes into plasma vectors and then transfected these vector clones into mammalian cells using a lipid-based transfection reagent. Following transient expression, the recombinant antibodies against LRRK2 were harvested and characterized. The recombinant LRRK2 antibody was purified by Affinity-chromatography from the culture medium. It can be used to detect LRRK2 protein from Human in the ELISA, IHC.

  • Uniprot No.：
  • 基因名：
  • 別名：
    Leucine-rich repeat serine/threonine-protein kinase 2 (EC 2.7.11.1) (Dardarin), LRRK2, PARK8
  • 反應(yīng)種屬：
    Human
  • 免疫原：
    A synthesized peptide derived from human LRRK2
  • 免疫原種屬：
    Homo sapiens (Human)
  • 標(biāo)記方式：
    Non-conjugated
  • 克隆類型：
    Monoclonal
  • 抗體亞型：
    Rabbit IgG
  • 純化方式：
    Affinity-chromatography
  • 克隆號：
    4E9
  • 濃度：
    It differs from different batches. Please contact us to confirm it.
  • 保存緩沖液：
    Rabbit IgG in phosphate buffered saline, pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol.
  • 產(chǎn)品提供形式：
    Liquid
  • 應(yīng)用范圍：
    ELISA, IHC
  • 推薦稀釋比：
    Application Recommended Dilution
    IHC 1:50-1:200
  • Protocols：
  • 儲存條件：
    Upon receipt, store at -20°C or -80°C. Avoid repeated freeze.
  • 貨期：
    Basically, we can dispatch the products out in 1-3 working days after receiving your orders. Delivery time maybe differs from different purchasing way or location, please kindly consult your local distributors for specific delivery time.

產(chǎn)品評價(jià)

靶點(diǎn)詳情

  • 功能：
    Serine/threonine-protein kinase which phosphorylates a broad range of proteins involved in multiple processes such as neuronal plasticity, autophagy, and vesicle trafficking. Is a key regulator of RAB GTPases by regulating the GTP/GDP exchange and interaction partners of RABs through phosphorylation. Phosphorylates RAB3A, RAB3B, RAB3C, RAB3D, RAB5A, RAB5B, RAB5C, RAB8A, RAB8B, RAB10, RAB12, RAB35, and RAB43. Regulates the RAB3IP-catalyzed GDP/GTP exchange for RAB8A through the phosphorylation of 'Thr-72' on RAB8A. Inhibits the interaction between RAB8A and GDI1 and/or GDI2 by phosphorylating 'Thr-72' on RAB8A. Regulates primary ciliogenesis through phosphorylation of RAB8A and RAB10, which promotes SHH signaling in the brain. Together with RAB29, plays a role in the retrograde trafficking pathway for recycling proteins, such as mannose-6-phosphate receptor (M6PR), between lysosomes and the Golgi apparatus in a retromer-dependent manner. Regulates neuronal process morphology in the intact central nervous system (CNS). Plays a role in synaptic vesicle trafficking. Plays an important role in recruiting SEC16A to endoplasmic reticulum exit sites (ERES) and in regulating ER to Golgi vesicle-mediated transport and ERES organization. Positively regulates autophagy through a calcium-dependent activation of the CaMKK/AMPK signaling pathway. The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes. Phosphorylates PRDX3. By phosphorylating APP on 'Thr-743', which promotes the production and the nuclear translocation of the APP intracellular domain (AICD), regulates dopaminergic neuron apoptosis. Independent of its kinase activity, inhibits the proteosomal degradation of MAPT, thus promoting MAPT oligomerization and secretion. In addition, has GTPase activity via its Roc domain which regulates LRRK2 kinase activity.
  • 基因功能參考文獻(xiàn)：
    1. G2019S carriers had a more benign phenotype than non-carriers and LRRK2 gene dosage does not influence the severity of Parkinson's disease PMID: 29989150
    2. The data of this study and the existing results strongly suggest that the autonomic features of manifesting LRRK2 mutation carriers are generally indistinguishable from those of sporadic Parkinson's disease. PMID: 28483388
    3. that the hemipterous pathway plays an important role in Lrrk2-linked Parkinsonism in flies PMID: 29268033
    4. Our findings reveal a new function of LRRK2 mediated by Rab8a phosphorylation and related to various centrosomal defects. PMID: 29357897
    5. This review summarizes the cellular function and pathophysiology of LRRK2 ROCO domain mutations in PD and the perspective of therapeutic approaches. PMID: 29903014
    6. Aging brain is more susceptible to LRRK2-associated pathology, and in this model, glial LRRK2 expression significantly contributed to neuroinflammation, ultimately causing neurodegeneration such as Parkinson's disease. PMID: 29550548
    7. LRRK2 R1398H or N551K variants do not appear to modulate the risk of Alzheimer's disease. PMID: 29241968
    8. Mutant LRRK2 disrupts synaptic vesicle endocytosis, leading to altered dopamine metabolism and dopamine-mediated toxic effects in patient-derived dopaminergic neurons. PMID: 29735704
    9. Rab8a is phosphorylated by LRRK2. PMID: 29482628
    10. Interrogating Parkinson's disease LRRK2 kinase pathway activity by assessing Rab10 phosphorylation in human neutrophils has been reported. PMID: 29127255
    11. In vivo activity of the LRRK2 Parkinson's disease kinase has been reported. PMID: 29127256
    12. Studied leucine rich repeat kinase 2 (LRRK2)-WAS protein family member 2 (WAVE2) pathway in modulation of phagocytosis in leukocytes, as well as its possible role for altered immune function in Parkinson's Disease. PMID: 29760073
    13. The LRRK2 mutation Gly2019Ser is the most common genetic cause of Parkinson's disease worldwide. PMID: 27751534
    14. we found that patients with Parkinson's disease who were carriers of the G2385R variant of the LRRK2 gene were more prone to fatigue than non-carriers PMID: 28941828
    15. These data indicate that mitochondrial deficits in the context of LRRK2 G2019S are not a global phenomenon and point to distinct sirtuin and bioenergetic deficiencies intrinsic to dopaminergic neurons, which may underlie dopaminergic neuron loss in Parkinson's disease. PMID: 29129681
    16. The G2019S-LRRK2 mutation upregulates LRRK2-kinase activity-dependent autophosphorylation at Ser1292 in exosomes captured from peripheral and brain-derived exosomes. LRRK2 protein in brain exosomes may be much more active than in the periphery in most subjects PMID: 29166931
    17. phosphorylation of LRRK2 following inhibitor treatment shows target engagement in peripheral mononuclear cells from Parkinson's disease patients PMID: 27503089
    18. Data indicate the generation of an Induced pluripotent stem cells (iPSCs)-based model of idiopathic Parkinson's disease (iPD) with or without RS1491923, which is a common risk variant in the leucine rich repeat kinase 2 (LRRK2) locus. PMID: 29513666
    19. These results implicate LRRK2 in primary ciliogenesis and suggest that Rab-mediated protein transport and/or signaling defects at cilia may contribute to LRRK2-dependent pathologies. PMID: 29125462
    20. Comparative analysis of motor and non-motor features in LRRK2 and GBA mutation carriers and non-carriers conducted in a cohort from Brazil, a country with a highly miscegenated population. Similarly to other studies, our results suggest that mutations in GBA and LRRK2 influence the clinical signs of the Parkinson's disease, with significant implications for handling of specific patient groups. PMID: 28991672
    21. that LRRK2 regulates the balance between WNT/beta-catenin and WNT/PCP signaling PMID: 28697798
    22. Study describes a distinctive genomic signature of neural and intestinal organoids from familial Parkinson's disease patient-derived induced pluripotent stem cells with leucine-rich repeat kinase 2 mutatiin (LK2GS) . Study provides the first evidence that LK2GS mutation also causes significant changes in gene expression in the intestinal cells. PMID: 28235153
    23. human induced pluripotent stem cells (hiPSCs) reprogrammed from skin fibroblasts of Parkinson's disease patients suffering from the LRKK2 G2019S mutation. PMID: 27640816
    24. S129P-alphaS plays a role in the maintenance or formation of long neurites. PMID: 28826027
    25. Nrf2 sequestered misfolded diffuse LRRK2 into more insoluble and homogeneous inclusion bodies. PMID: 28028237
    26. R1628P variant of LRRK2 has a significant association with the risk of PD. PMID: 27812003
    27. Mild cognitive impairment may appear earlier than motor dysfunctions in LRRK2-G2019S mutation carriers. PMID: 28487191
    28. Authors found that HOTAIR was up-regulated in midbrain tissue of MTPT induced PD mice and in SH-SY5Y cells exposed to MPP+. With the presence of HOTAIR overexpression in SH-SY5Y cells, the expression of LRRK2 was increased compared with that in the control. PMID: 28445933
    29. Findings support the hypothesis that LRRK2 G2019S-induced mtDNA damage is LRRK2 kinase activity dependent, uncovering a novel pathological role for this kinase. PMID: 28973664
    30. Author demonstrated that LRRK2 increases the expression of p53 and p21 by increasing the Mdm2 phosphorylation in response to DNA damage. Loss-of-function in LRRK2 has the opposite effect to that of LRRK2. PMID: 28973420
    31. report that LRRK2(G2019S) mutation carriers with Parkinson's disease exhibit a high concentration of mitochondrial DNA in cerebrospinal fluid PMID: 27260835
    32. The results of this study suggest that mutations on specific genes (PARK2 and LRRK2) compromising basal ganglia functioning may be subtly related to language-processing mechanisms. PMID: 28205494
    33. Mutations in leucine-rich repeat kinase 2 (LRRK2) are the major genetic cause of autosomal-dominantly inherited Parkinson's disease. LRRK2 is implicated in the regulation of intracellular trafficking, neurite outgrowth and PD risk in connection with Rab7L1, a putative interactor of LRRK2. The modulation of Ser72 phosphorylation in Rab7L1 resulted in an alteration of the trans-Golgi network. PMID: 29223392
    34. This study identified five microRNAs that play a role in the etiology of Parkinson's disease likely by modifying expression of LRRK2 and additional genes required for normal cellular function. PMID: 27717584
    35. Thus study shown LRRK2 does not appear to play a major role in dementia with Lewy bodies. PMID: 27521182
    36. LRRK2-induced apoptosis was suppressed by ASK1 inhibition in neuronal stem cells derived from patients with Parkinson's disease (PD). These results clearly indicate that LRRK2 acts as an upstream kinase in the ASK1 pathway and plays an important role in the pathogenesis of PD PMID: 28888991
    37. The results of this study revealed clinical heterogeneity of the LRRK2 p.I2012T substitution, and demonstrated the use of targeted NGS for genetic diagnosis in multiplex families with PD or mixed neurodegenerative disorders. PMID: 27628070
    38. Parkinson's disease is associated with mutations in LRRK2 gene in Ashkenazi Jews. PMID: 27449028
    39. Data elucidate the mechanism underlying the increased microtubules association of select pathogenic LRRK2 mutants or of pharmacologically kinase-inhibited LRRK2, with implications for downstream microtubule-mediated transport events. PMID: 28453723
    40. Inflammation seems to be associated with the presence of a specific clinical subtype in PDLRRK2 that is characterized by a broad and more severely affected spectrum of motor and non-motor symptoms PMID: 28102045
    41. R1628P polymorphism of the LRRK2 gene contributes to Parkinson's disease susceptibility in Asian, especially Chinese, populations.[meta-analysis] PMID: 27384489
    42. In contrast to PD, common LRRK2 variants do not appear to play a major role in determining PSP and corticobasal degeneration risk. PMID: 27709685
    43. G2385R and G2019S Parkinson's disease appear to have motor differences PMID: 27091104
    44. LRRK2 regulates intracellular Tau levels, contributing to the progression of the pathology caused by the LRRK2-mediated proteasome impairment. PMID: 26014385
    45. The G2019S mutation is associated with increased asymmetry and variability among nonmanifesting participants and patients with PD. PMID: 27430880
    46. Peripheral inflammation is higher in a percentage of Parkinson subjects carrying the LRRK2 G2019S mutation. PMID: 26917005
    47. The CSF protein profile differs in LRRK2-associated PD and idiopathic PD, suggesting that pathophysiological mechanisms different from IPD underlie LRRK2-associated PD. PMID: 27041685
    48. Asymptomatic LRRK2 mutation carriers showed functional connectivity changes in striatocortical and nigrocortical circuits compared with noncarriers. PMID: 27653520
    49. LRRK2 transgenic mice develop motor impairment and selective activation of CB2 receptor partially reversed the deficits. PMID: 27063942
    50. Study found elevated LRRK2 levels in CD14++ and CD16+ monocyte subsets of Parkinson's disease patients, but not in patients' B-cells; and a dysregulation of monocyte subpopulations was detected in LRRK2 overexpressing mice. PMID: 27884177

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  • 相關(guān)疾病：
    Parkinson disease 8 (PARK8)
  • 亞細(xì)胞定位：
    Cytoplasmic vesicle. Perikaryon. Golgi apparatus membrane; Peripheral membrane protein. Cell projection, axon. Cell projection, dendrite. Endoplasmic reticulum membrane; Peripheral membrane protein. Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane. Endosome. Lysosome. Mitochondrion outer membrane; Peripheral membrane protein.
  • 蛋白家族：
    Protein kinase superfamily, TKL Ser/Thr protein kinase family
  • 組織特異性：
    Expressed in pyramidal neurons in all cortical laminae of the visual cortex, in neurons of the substantia nigra pars compacta and caudate putamen (at protein level). Expressed in neutrophils (at protein level). Expressed in the brain. Expressed throughout
  • 數(shù)據(jù)庫鏈接：

    HGNC: 18618

    OMIM: 168600

    KEGG: hsa:120892

    STRING: 9606.ENSP00000298910

    UniGene: Hs.187636