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2. 发明申请

WO9824810A2 VERTEBRATE HOMOLOGUES OF UNC-53 PROTEIN OF C. ELEGANS 审中-公开
标题翻译： C.ELEGANS的UNC-53蛋白的VERTEBRATE HOMOLOGUES
公开(公告)号：WO9824810A2
公开(公告)日：1998-06-11
申请号：PCT/EP9706956
申请日：1997-12-03
申请人： JANSSEN PHARMACEUTICA NV , PLATTEEUW CHRIST JULES , BUESA ARJOL CARLOS MANUEL , DERAEYMAEKER MARC , VERHASSELT PETER , PUJOL NATHALIE JEANNE RAYMONDE , MAERTENS LUC JACQUES SIMON , LUYTEN WALTER , GEERTS HUGO , VANDEKERCKHOVE JOEL STEFAAN , GEYSEN JOHAN , BOGAERT THIERRY ANDRE OLIVIER
发明人： PLATTEEUW CHRIST JULES , BUESA ARJOL CARLOS MANUEL , DERAEYMAEKER MARC , VERHASSELT PETER , PUJOL NATHALIE JEANNE RAYMONDE , MAERTENS LUC JACQUES SIMON , LUYTEN WALTER , GEERTS HUGO , VANDEKERCKHOVE JOEL STEFAAN , GEYSEN JOHAN , BOGAERT THIERRY ANDRE OLIVIER
IPC分类号： C12N15/09 , A61K38/00 , A61K45/00 , A61K48/00 , A61P25/00 , A61P43/00 , C07K14/435 , C07K14/46 , C07K14/47 , C07K16/18 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12P21/02 , C12P21/08 , C12Q1/02 , C12Q1/68 , C12R1/91 , C07K14/00
CPC分类号： C07K14/47 , A61K38/00
摘要： Vertebrate protein homologues of UNC-53 protein of C. elegans and nucleic acid sequences coding for said homologues or functional equivalents thereof are identified. The nucleic acid sequences in an appropriate vector are used to transfect or transform cells, tissues or organisms useful in identifying inhibitors or enhancers of the vertebrate homologue, or further proteins involved in the signal transduction pathway of which said vertebrate homologue is a component. Any of said inhibitors or enhancers identified can be included in a pharmaceutical composition or in the preparation of a medicament for treating conditions such as neurological diseases, acute traumatic injuries and to promote neuronal regeneration and inhibit metastasis or loss of contact inhibition.
摘要翻译：鉴定了秀丽隐杆线虫UNC-53蛋白的脊椎动物蛋白同源物和编码所述同源物或其功能等同物的核酸序列。适当载体中的核酸序列用于转染或转化用于鉴定脊椎动物同源物的抑制剂或增强子的细胞，组织或生物体，或涉及其中所述脊椎动物同系物是组分的信号转导途径的其它蛋白质。鉴定的所述抑制剂或增强剂中的任何一种可以包括在药物组合物中或制备用于治疗诸如神经系统疾病，急性外伤性损伤之类的疾病的药物中，并促进神经元再生和抑制转移或接触抑制丧失。

3. 发明申请

WO0007014A3 LEPTIN-MEDIATED GENE-INDUCTION 审中-公开
标题翻译： LEPTIN介导的基因诱导
公开(公告)号：WO0007014A3
公开(公告)日：2000-04-27
申请号：PCT/EP9905489
申请日：1999-07-27
申请人： VLAAMS INTERUNIV INST BIOTECH , BROEKAERT DANIEL , VANDEKERCKHOVE JOEL STEFAAN , VERHEE ANNICK , WAELPUT WIM , TAVERNIER JAN
发明人： BROEKAERT DANIEL , VANDEKERCKHOVE JOEL STEFAAN , VERHEE ANNICK , WAELPUT WIM , TAVERNIER JAN
IPC分类号： G01N33/50 , A61K31/22 , A61K38/00 , A61K38/19 , A61K38/22 , A61K45/00 , A61P3/00 , A61P3/04 , A61P37/00 , A61P43/00 , C07K14/575 , C12N15/09 , C12Q1/68 , C12R1/91 , G01N33/15
CPC分类号： C07K14/5759 , A61K38/2264 , A61K2300/00
摘要： Using the PC12 cell line as a model system a series of transcripts induced through activation of the leptin receptor or gp130 was identified. Based on kinetic studies on undifferentiated PC12 cells, two distinct gene-sets could be discerned: STAT-3, SOCS-3, Metallothionein-II, the serine/threonine kinase Fnk and the rat homologue of MRF-1 which are immediate early response genes, and Pancreatitis Associated Protein I, Squalene Epoxidase, Uridinediphosphate Glucuronyl Transferase and Annexin VIII, which are late induced target genes. In the latter case only, a strong co-stimulation with the adenylate cyclase activator forskolin was observed. Two additional transcripts encoding Leptin Induced Protein I (LIP-I) and Leptin Induced Protein II (LIP-II) were also identified. LIP-II is a rat orthologue of the human Down Syndrome Cell Adhesion Molecule (DS-CAM). In both cases, no forskolin co-stimulatory effect was observed. On PC12 cells differentiated to a neural phenotype by combined beta -NGF and forskolin treatment, Pancreatitis Associated Protein III, Peripherin and Mx2 protein were further identified as being regulated by leptin. Finally, from an RDA experiment using mRNA from either hyper-IL-6- or leptin-induced PC12 cells, the Reg gene, another member of the Pancreatitis Associated Protein family, and HIP-1 were identified as selectively up-regulated by H-IL-6. STAT-3 and SOCS-3 have been recognized in leptin signalling in vivo before. In this invention it is also demonstrated that leptin modulates the in vivo expression of the MT-II, Fnk and Pancreatitis Associated Protein I genes.
摘要翻译：使用PC12细胞系作为模型系统，鉴定了通过激活瘦蛋白受体或gp130诱导的一系列转录物。基于对未分化PC12细胞的动力学研究，可以看出两个不同的基因组：STAT-3，SOCS-3，金属硫蛋白II，丝氨酸/苏氨酸激酶Fnk和MRF-1的大鼠同源物，其是即时早期应答基因，胰腺炎相关蛋白I，角鲨烯环氧酶，二叉二磷酸葡萄糖醛酸转移酶和膜联蛋白VIII，它们是晚期诱导的靶基因。仅在后一种情况下，观察到与腺苷酸环化酶激活剂毛喉素的强共刺激。还鉴定了编码瘦素诱导蛋白I（LIP-I）和瘦蛋白诱导蛋白II（LIP-II）的另外两个转录物。 LIP-II是人类唐氏综合征细胞粘附分子（DS-CAM）的大鼠直向同源物。在两种情况下，没有观察到毛喉素共刺激作用。在通过联合β-NGF和毛喉素处理分化为神经表型的PC12细胞上，胰腺炎相关蛋白III，Peripherin和Mx2蛋白被进一步鉴定为被瘦蛋白调节。最后，从使用来自高IL-6或瘦素诱导的PC12细胞的mRNA的RDA实验中，鉴定出胰岛素相关蛋白家族的另一成员Reg基因和HIP-1被选择性上调H- IL-6。 STAT-3和SOCS-3已被体内瘦素信号传导。在本发明中，还证明瘦素调节MT-II，Fnk和胰腺炎相关蛋白I基因的体内表达。

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