公开(公告)号：US06528270B1

公开(公告)日：2003-03-04

申请号：US09393585

申请日：1999-09-09

申请人： Joseph Schlessinger ,  Mikhail L. Gishizky ,  Ann Marie Pendergast

发明人： Joseph Schlessinger ,  Mikhail L. Gishizky ,  Ann Marie Pendergast

IPC分类号： G01N3355

CPC分类号： G01N33/5005 ,  A61K38/00 ,  C07K14/4705 ,  C07K14/82 ,  G01N33/5008 ,  G01N33/5011 ,  G01N33/5041 ,  G01N33/573 ,  G01N33/68

摘要： The present invention relates to compositions and methods for the prevention and treatment of cell proliferative disorders wherein a protein tyrosine kinase or protein tyrosine phosphatase capable of complexing with a member of the SH2- and/or SH3-containing family of adaptor proteins is involved. This invention is based, in part, on the surprising discovery that the adaptor protein, GRB-2, binds the intracellular BCR-ABL tyrosine kinase product in vivo and is necessary for the activation of the oncogenic potential of the BCR/ABL product. The present invention further relates to protein tyrosine kinase/adaptor protein complexes and the uses of these complexes for the identification of agents capable of decreasing or inhibiting the interaction between the members of such complexes.

摘要翻译： 本发明涉及用于预防和治疗细胞增殖性疾病的组合物和方法，其中涉及能够与适配蛋白家族的含SH2-和/或SH3的成员配合的蛋白质酪氨酸激酶或蛋白质酪氨酸磷酸酶。 本发明部分基于令人惊奇的发现，即接头蛋白GRB-2在体内结合细胞内BCR-ABL酪氨酸激酶产物，并且是激活BCR / ABL产物的致癌潜力所必需的。 本发明还涉及蛋白质酪氨酸激酶/衔接蛋白复合物以及这些复合物用于鉴定能够降低或抑制这些复合物成员之间相互作用的试剂的用途。

公开(公告)号：US6054280A

公开(公告)日：2000-04-25

申请号：US407165

申请日：1995-03-20

申请人： Mark A. Lemmon ,  Kathryn M. Ferguson ,  Paul B. Sigler ,  Joseph Schlessinger

发明人： Mark A. Lemmon ,  Kathryn M. Ferguson ,  Paul B. Sigler ,  Joseph Schlessinger

IPC分类号： G01N33/68 ,  G01N33/53

CPC分类号： A61K31/6615 ,  G01N33/6896 ,  G01N2500/20

摘要： Methods for treatment, diagnosis, and screening are provided for diseases or conditions characterized by an abnormality in a signal transduction disorder. The signal transduction pathway involves an interaction between a PH domain and a PH domain binding partner.

摘要翻译： 提供治疗，诊断和筛查的方法用于以信号转导障碍异常为特征的疾病或病症。 信号转导途径涉及PH结构域和PH结构域结合配偶体之间的相互作用。

公开(公告)号：US5942428A

公开(公告)日：1999-08-24

申请号：US701191

申请日：1996-08-21

申请人： Moosa Mohammadi ,  Joseph Schlessinger ,  Stevan R. Hubbard

发明人： Moosa Mohammadi ,  Joseph Schlessinger ,  Stevan R. Hubbard

IPC分类号： C07K14/71 ,  C12N9/12 ,  G01N33/68 ,  C07K14/705

CPC分类号： G01N33/6842 ,  C07K14/71 ,  C12N9/1205 ,  G01N33/68

摘要： Crystals of the tyrosine kinase domain of cytoplasmic tyrosine kinases and receptor tyrosine kinases that undergo ligand-mediated receptor dimerization are provided. In particular, crystals of a mutant of the tyrosine kinase domain of fibroblast growth factor receptor 1 (FLGK), alone and in complex with a non-hydrolyzable adenosine triphosphate analogue, are provided. Also provided are the high resolution three dimensional structures of crystalline FLGK, both alone and in co-complex with the adenosine triphosphate analogue, as determined by X-ray diffraction.

摘要翻译： 提供了经历配体介导的受体二聚化的细胞质酪氨酸激酶和受体酪氨酸激酶的酪氨酸激酶结构域的晶体。 特别地，提供单独的和与不可水解的三磷酸腺苷类似物复合的成纤维细胞生长因子受体1（FLGK）的酪氨酸激酶结构域的突变体的晶体。 还提供了通过X射线衍射测定的结晶FLGK的单分辨率和与三磷酸腺苷类似物的共配合物的高分辨率三维结构。

公开(公告)号：US5856162A

公开(公告)日：1999-01-05

申请号：US449644

申请日：1995-05-24

申请人： Joseph Schlessinger ,  Jan M. Sap ,  Axel Ullrich ,  Wolfgang Vogel ,  Miriam Fuchs

发明人： Joseph Schlessinger ,  Jan M. Sap ,  Axel Ullrich ,  Wolfgang Vogel ,  Miriam Fuchs

IPC分类号： G01N33/50 ,  A61K39/395 ,  A61K45/00 ,  C07H21/04 ,  C07K14/705 ,  C07K16/18 ,  C12N5/00 ,  C12N5/10 ,  C12N9/16 ,  C12N15/00 ,  C12N15/02 ,  C12P21/08 ,  C12Q1/68 ,  C12R1/91 ,  C12N15/52

CPC分类号： C12N9/16 ,  C07K14/705

摘要： A novel receptor-type protein tyrosine phosphatase-.kappa. (RPTP.kappa.) protein or glycoprotein and the DNA coding therefor is expressed in a wide variety of mammalian tissues. The RPTP.kappa. protein or glycoprotein may be produced by recombinant means. Antibodies to the protein, methods for measuring the quantity of the protein, methods for screening compounds, such as drugs, which can bind to the protein and inhibit or stimulate their enzymatic activity, are provided. Further, methods for inhibiting homophilic binding of Type II RPTP, especially RPTP.kappa. molecules are provided.

摘要翻译： 新型受体型蛋白酪氨酸磷酸酶κ（RPTP kappa）蛋白或糖蛋白及其编码的DNA在多种哺乳动物组织中表达。 可以通过重组方法产生RPTPκB蛋白或糖蛋白。 提供了对蛋白质的抗体，用于测量蛋白质量的方法，用于筛选可结合蛋白质并抑制或刺激其酶活性的化合物（例如药物）的方法。 此外，提供了用于抑制II型RPTP，特别是RPTPκ分子的亲和结合的方法。

公开(公告)号：US5807989A

公开(公告)日：1998-09-15

申请号：US363215

申请日：1994-12-23

申请人： Benjamin Lewis Margolis ,  Joseph Schlessinger ,  Vijay Yajnik

发明人： Benjamin Lewis Margolis ,  Joseph Schlessinger ,  Vijay Yajnik

IPC分类号： A61K38/00 ,  C07K14/71 ,  C07K4/12 ,  C07K5/00

CPC分类号： C07K14/71 ,  A61K38/00 ,  C07K2319/00

摘要： The present invention concerns methods for diagnosis and treatment of diseases or disorders characterized by abnormal cellular signal transduction involving a newly identified region, herein termed the "APB domain." APB domain binding between proteins is believed to play an important role in signal transduction pathways and, thereby, influence cellular events. Thus, APB mediated activity plays a role in signal transduction pathways and agents modulating APB mediated activity can be used to treat diseases or disorders involving proteins containing APB domains.

摘要翻译： 本发明涉及用于诊断和治疗特征在于涉及新鉴定区域的异常细胞信号转导的疾病或病症的方法，这里称为“APB结构域”。 认为蛋白质之间的APB结构域结合在信号转导途径中起重要作用，从而影响细胞事件。 因此，APB介导的活性在信号转导途径中起作用，并且调节APB介导的活性的试剂可用于治疗涉及含有APB结构域的蛋白质的疾病或病症。

公开(公告)号：US5538886A

公开(公告)日：1996-07-23

申请号：US15985

申请日：1993-02-10

申请人： Joseph Schlessinger ,  Jan M. Sap

发明人： Joseph Schlessinger ,  Jan M. Sap

IPC分类号： C07K14/705 ,  C12N9/16 ,  C12N15/55 ,  C12N1/21 ,  C12N5/10 ,  C12N15/63

CPC分类号： C07K14/705 ,  C12N9/16

摘要： A novel receptor-type protein tyrosine phosphatase (RPTP) protein or glycoprotein and the DNA coding therefor is expressed in a wide variety of mammalian tissues. Included in this family of proteins are human RPTP.alpha., human RPTP.beta. and human RPTP.gamma.. The RPTP protein or glycoprotein may be produced by recombinant means. Antibodies to the proteins, methods for measuring the quantity of the proteins, methods for screening compounds, such as drugs, which can bind to the proteins and inhibit or stimulate their activity, are provided.

公开(公告)号：US5532123A

公开(公告)日：1996-07-02

申请号：US15986

申请日：1993-02-10

申请人： Joseph Schlessinger

发明人： Joseph Schlessinger

IPC分类号： G01N33/50 ,  A61K38/00 ,  A61K39/395 ,  C07H21/04 ,  C07K14/00 ,  C07K14/47 ,  C07K14/705 ,  C07K16/00 ,  C07K16/28 ,  C12N1/19 ,  C12N1/21 ,  C12N5/10 ,  C12N9/16 ,  C12N15/09 ,  C12N15/55 ,  C12P21/02 ,  C12P21/08 ,  C12Q1/42 ,  C12Q1/68 ,  G01N33/15 ,  G01N33/53 ,  G01N33/566 ,  G01N33/573 ,  G01N33/577 ,  C12N15/63

CPC分类号： C12N9/16 ,  C07K14/705 ,  A61K38/00

摘要： A novel receptor-type protein tyrosine phosphatase-.gamma. (RPTP.gamma.) protein or glycoprotein and the DNA coding therefor is expressed in a wide variety of mammalian tissues. The RPTP.gamma. protein or glycoprotein may be produced by recombinant means. Antibodies to the protein, methods for measuring the quantity of the protein, methods for screening compounds, such as drugs, which can bind to the protein and inhibit or stimulate their enzymatic activity, are provided.