公开(公告)号：US20100151483A1

公开(公告)日：2010-06-17

申请号：US12309312

申请日：2007-07-13

申请人： Peter Hornbeck ,  Valerie Goss ,  Kimberly Lee ,  Ting-Lei Gu ,  Albrecht Moritz

发明人： Peter Hornbeck ,  Valerie Goss ,  Kimberly Lee ,  Ting-Lei Gu ,  Albrecht Moritz

IPC分类号： G01N33/53 ,  C07K16/18

CPC分类号： G01N33/68 ,  C07K16/18 ,  C07K16/32 ,  C07K16/40 ,  G01N33/60 ,  G01N33/6842 ,  G01N33/6845 ,  G01N33/6848

摘要： The invention discloses novel phosphorylation sites identified in signal transduction proteins and pathways, and provides phosphorylation-site specific antibodies and heavy-isotope labeled peptides (AQUA peptides) for the selective detection and quantification of these phosphorylated sites/proteins, as well as methods of using the reagents for such purpose. Among the phosphorylation sites identified are sites occurring in the following protein types: adaptor/scaffold proteins, adhesion/extracellular matrix protein, apoptosis proteins, calcium binding proteins, cell cycle regulation proteins, chaperone proteins, chromatin, DNA binding/repair/replication proteins, cytoskeletal proteins, endoplasmic reticulum or golgi proteins, enzyme proteins, G/regulator proteins, inhibitor proteins, motor/contractile proteins, phosphatase, protease, Ser/Thr protein kinases, protein kinase (Tyr)s, receptor/channel/cell surface proteins, RNA binding proteins, transcriptional regulators, tumor suppressor proteins, ubiquitan conjugating system proteins and proteins of unknown function.

摘要翻译： 本发明公开了在信号转导蛋白和途径中鉴定的新型磷酸化位点，并提供磷酸化位点特异性抗体和重同位素标记肽（AQUA肽），用于选择性检测和定量这些磷酸化位点/蛋白质，以及使用 用于此目的的试剂。 鉴定的磷酸化位点是发生在以下蛋白质类型中的位点：衔接子/支架蛋白，粘附/细胞外基质蛋白，凋亡蛋白，钙结合蛋白，细胞周期调节蛋白，伴侣蛋白，染色质，DNA结合/修复/复制蛋白， 细胞骨架蛋白，内质网或高尔基体蛋白，酶蛋白，G /调节蛋白，抑制蛋白，运动/收缩蛋白，磷酸酶，蛋白酶，Ser / Thr蛋白激酶，蛋白激酶（Tyr），受体/通道/细胞表面蛋白， RNA结合蛋白，转录调节物，肿瘤抑制蛋白，泛素偶联系统蛋白和功能未知的蛋白。

公开(公告)号：US07888480B2

公开(公告)日：2011-02-15

申请号：US12074224

申请日：2008-02-29

申请人： Roberto Polakiewicz ,  Valerie Goss ,  Albrecht Moritz ,  Ting-Lei Gu ,  Kimberly Lee

发明人： Roberto Polakiewicz ,  Valerie Goss ,  Albrecht Moritz ,  Ting-Lei Gu ,  Kimberly Lee

IPC分类号： C07K16/00

CPC分类号： G01N33/6842 ,  C07K16/3061 ,  C07K16/44 ,  C07K2317/34 ,  G01N33/57426 ,  G01N2458/15

摘要： The invention discloses nearly 288 novel phosphorylation sites identified in signal transduction proteins and pathways underlying human Leukemia, and provides phosphorylation-site specific antibodies and heavy-isotope labeled peptides (AQUA peptides) for the selective detection and quantification of these phosphorylated sites/proteins, as well as methods of using the reagents for such purpose. Among the phosphorylation sites identified are sites occurring in the following protein types: Adaptor/Scaffold proteins, Cytoskeletal proteins, Cellular Metabolism enzymes, G Protein/GTPase Activating/Guanine Nucleotide Exchange Factor proteins, Immunoglobulin Superfamily proteins, Inhibitor proteins, Lipid Kinases, Nuclear DNA Repair/RNA Binding/Transcription proteins, Serine/Threonine Protein Kinases, Tyrosine Kinases, Protein Phosphatases, and Translation/Transporter proteins.

摘要翻译： 本发明公开了在信号转导蛋白中鉴定的近288个新的磷酸化位点和人类白血病潜在的途径，并提供磷酸化位点特异性抗体和重同位素标记肽（AQUA肽），用于选择性检测和定量这些磷酸化位点/蛋白质，如 以及使用试剂用于此目的的方法。 所鉴定的磷酸化位点是以下蛋白质类型的位点：适配器/支架蛋白，细胞骨架蛋白，细胞代谢酶，G蛋白/ GTP酶激活/鸟嘌呤核苷酸交换因子蛋白，免疫球蛋白超家族蛋白，抑制蛋白，脂质激酶，核DNA 修复/ RNA结合/转录蛋白，丝氨酸/苏氨酸蛋白激酶，酪氨酸激酶，蛋白磷酸酶和翻译/转运蛋白。

公开(公告)号：US20100093008A1

公开(公告)日：2010-04-15

申请号：US11681521

申请日：2007-03-02

申请人： Valerie GOSS ,  Roberto Polakiewicz ,  Kimberly Lee ,  Ting-Lei Gu ,  Albrecht Moritz ,  Jiong Wu

发明人： Valerie GOSS ,  Roberto Polakiewicz ,  Kimberly Lee ,  Ting-Lei Gu ,  Albrecht Moritz ,  Jiong Wu

IPC分类号： C12Q1/48 ,  C07K16/40 ,  C12N5/12

CPC分类号： G01N33/573 ,  C07K16/2863 ,  C07K16/44 ,  C07K2317/34 ,  G01N33/57426 ,  G01N2333/9121 ,  G01N2800/52

摘要： The invention discloses a newly discovered Flt3 phosphorylation site, tyrosine 969 (Tyr969) in the intracellular domain, and provides reagents, including polyclonal and monoclonal antibodies, that selectively bind to Flt3 when phosphorylated at this site. Also provided are assays utilizing this reagent, including methods for determining the phosphorylation of Flt3 in a biological sample, selecting a patient suitable for Flt3 inhibitor therapy, profiling Flt3 activation in a test tissue, and identifying a compound that modulates phosphorylation of Flt3 in a test tissue, by using a detectable reagent, such as the disclosed antibody, that binds to Flt3 only when phosphorylated at Tyr969. The sample or test tissue may be taken from a subject suspected of having cancer, such as acute myelogenous leukemia (AML).

摘要翻译： 本发明公开了新发现的Flt3磷酸化位点，细胞内结构域中的酪氨酸969（Tyr969），并提供了在该位点磷酸化时选择性结合Flt3的试剂，包括多克隆和单克隆抗体。 还提供了使用该试剂的测定法，包括用于测定生物样品中Flt3的磷酸化的方法，选择适合Flt3抑制剂治疗的患者，在测试组织中分析Flt3活化，以及鉴定在测试中调节Flt3的磷酸化的化合物 通过使用仅在Tyr969磷酸化时与Flt3结合的可检测试剂，例如所公开的抗体。 样品或测试组织可以从疑似患有癌症的受试者中获取，例如急性骨髓性白血病（AML）。

公开(公告)号：US20090220991A1

公开(公告)日：2009-09-03

申请号：US12074214

申请日：2008-02-29

申请人： Roberto Polakiewicz ,  Valerie Goss ,  Albrecht Moritz ,  Ting-Lei Gu ,  Kimberly Lee

发明人： Roberto Polakiewicz ,  Valerie Goss ,  Albrecht Moritz ,  Ting-Lei Gu ,  Kimberly Lee

IPC分类号： G01N33/53 ,  G01N33/536 ,  C07K16/18 ,  C12N5/18

CPC分类号： C07K16/40 ,  C07K16/18 ,  C07K16/2803 ,  C07K16/2896 ,  C07K16/3061 ,  C07K2317/34 ,  G01N33/57426 ,  G01N33/6854

摘要： The invention discloses nearly 480 novel phosphorylation sites identified in signal transduction proteins and pathways underlying human Leukemia, and provides phosphorylation site specific antibodies and heavy-isotope labeled peptides (AQUA peptides) for the selective detection and quantification of these phosphorylated sites/proteins, as well as methods of using the reagents for such purpose. Among the phosphorylation sites identified are sites occurring in the following protein types: adaptor/scaffold proteins, acetyltransferases, actin binding proteins, adhesion proteins, apoptosis proteins, calcium-binding proteins, cell cycle regulation proteins, cell surface proteins, channel proteins, chaperone proteins, contractile proteins, cytokine proteins, cytoskeletal proteins, G protein regulators and GTPase activating proteins, guanine nucleotide exchange factors, helicase proteins, immunoglobulin superfamily proteins, inhibitor proteins, protein kinases, lipid kinases, ligases, lipid binding proteins, methytransferases, motor proteins, oxidoreductases, phosphotases, phosphodiesterases, phospholipases, proteases, receptor proteins, trascription factors, transferases, translation/transporter proteins, and ubiquitin conjugating system proteins.

摘要翻译： 本发明公开了在信号转导蛋白中识别的近480个新的磷酸化位点和人类白血病下游的途径，并提供磷酸化位点特异性抗体和重同位素标记肽（AQUA肽），用于选择性检测和定量这些磷酸化位点/蛋白质 作为使用试剂用于此目的的方法。 鉴定的磷酸化位点是发生在以下蛋白质类型中的位点：衔接子/支架蛋白，乙酰转移酶，肌动蛋白结合蛋白，粘附蛋白，凋亡蛋白，钙结合蛋白，细胞周期调节蛋白，细胞表面蛋白，通道蛋白，伴侣蛋白 鸟嘌呤核苷酸交换因子，解旋酶蛋白，免疫球蛋白超家族蛋白，抑制蛋白，蛋白激酶，脂质激酶，连接酶，脂质结合蛋白，甲基转移酶，运动蛋白，肌动蛋白， 氧化还原酶，磷酸二酯酶，磷脂酶，蛋白酶，受体蛋白，trascription因子，转移酶，翻译/转运蛋白和泛素缀合系统蛋白。

公开(公告)号：US07999080B2

公开(公告)日：2011-08-16

申请号：US12309310

申请日：2007-07-13

申请人： Peter Hornbeck ,  Valerie Goss ,  Kimberly Lee ,  Ting-Lei Gu ,  Albrecht Moritz

发明人： Peter Hornbeck ,  Valerie Goss ,  Kimberly Lee ,  Ting-Lei Gu ,  Albrecht Moritz

IPC分类号： C07K16/18

CPC分类号： C12Q1/485 ,  C07K16/18 ,  C07K16/40 ,  C07K16/44 ,  G01N33/68 ,  G01N33/6842 ,  G01N33/6845 ,  G01N33/6848 ,  G01N33/6872

摘要： The invention discloses novel phosphorylation sites identified in signal transduction proteins and pathways, and provides phosphorylation-site specific antibodies and heavy-isotope labeled peptides (AQUA peptides) for the selective detection and quantification of these phosphorylated sites/proteins, as well as methods of using the reagents for such purpose. Among the phosphorylation sites identified are sites occurring in the following protein types: adaptor/scaffold proteins, adhesion/extracellular matrix protein, apoptosis proteins, calcium binding proteins, cell cycle regulation proteins, chaperone proteins, chromatin, DNA binding/repair/replication proteins, cytoskeletal proteins, endoplasmic reticulum or golgi proteins, enzyme proteins, G/regulator proteins, inhibitor proteins, motor/contractile proteins, phosphatase, protease, Ser/Thr protein kinases, Protein kinase (Tyr)s, receptor/channel/cell surface proteins, RNA binding proteins, transcriptional regulators, tumor suppressor proteins, ubiquitan conjugating system proteins and proteins of unknown function.

摘要翻译： 本发明公开了在信号转导蛋白和途径中鉴定的新型磷酸化位点，并提供磷酸化位点特异性抗体和重同位素标记肽（AQUA肽），用于选择性检测和定量这些磷酸化位点/蛋白质，以及使用 用于此目的的试剂。 鉴定的磷酸化位点是发生在以下蛋白质类型中的位点：衔接子/支架蛋白，粘附/细胞外基质蛋白，凋亡蛋白，钙结合蛋白，细胞周期调节蛋白，伴侣蛋白，染色质，DNA结合/修复/复制蛋白， 细胞骨架蛋白，内质网或高尔基体蛋白，酶蛋白，G /调节蛋白，抑制蛋白，运动/收缩蛋白，磷酸酶，蛋白酶，Ser / Thr蛋白激酶，蛋白激酶（Tyr），受体/通道/细胞表面蛋白， RNA结合蛋白，转录调节物，肿瘤抑制蛋白，泛素偶联系统蛋白和功能未知的蛋白。

公开(公告)号：US20100009463A1

公开(公告)日：2010-01-14

申请号：US12309313

申请日：2007-07-13

申请人： Peter Hornbeck ,  Valerie Goss ,  Kimberly Lee ,  Ting-Lei Gu ,  Albrecht Moritz

发明人： Peter Hornbeck ,  Valerie Goss ,  Kimberly Lee ,  Ting-Lei Gu ,  Albrecht Moritz

IPC分类号： G01N33/566 ,  C07K16/18 ,  C07K14/47 ,  C12N5/16 ,  C12N5/18

CPC分类号： G01N33/57426 ,  C07B59/008 ,  C07K14/47 ,  C07K16/44 ,  G01N33/6842 ,  G01N2458/15

摘要： The invention discloses novel phosphorylation sites identified in signal transduction proteins and pathways, and provides phosphorylation-site specific antibodies and heavy-isotope labeled peptides (AQUA peptides) for the selective detection and quantification of these phosphorylated sites/proteins, as well as methods of using the reagents for such purpose. Among the phosphorylation sites identified are sites occurring in the following protein types: adaptor/scaffold proteins, adhesion/extracellular matrix protein, apoptosis proteins, calcium binding proteins, cell cycle regulation proteins, chaperone proteins, chromatin, DNA binding/repair/replication proteins, cytoskeletal proteins, endoplasmic reticulum or golgi proteins, enzyme proteins, G/regulator proteins, inhibitor proteins, motor/contractile proteins, phosphatase, protease, Ser/Thr protein kinases, protein kinase (Tyr)s, receptor/channel/cell surface proteins, RNA binding proteins, transcriptional regulators, tumor suppressor proteins, ubiquitan conjugating system proteins and proteins of unknown function.

摘要翻译： 本发明公开了在信号转导蛋白和途径中鉴定的新型磷酸化位点，并提供磷酸化位点特异性抗体和重同位素标记肽（AQUA肽），用于选择性检测和定量这些磷酸化位点/蛋白质，以及使用 用于此目的的试剂。 鉴定的磷酸化位点是发生在以下蛋白质类型中的位点：衔接子/支架蛋白，粘附/细胞外基质蛋白，凋亡蛋白，钙结合蛋白，细胞周期调节蛋白，伴侣蛋白，染色质，DNA结合/修复/复制蛋白， 细胞骨架蛋白，内质网或高尔基体蛋白，酶蛋白，G /调节蛋白，抑制蛋白，运动/收缩蛋白，磷酸酶，蛋白酶，Ser / Thr蛋白激酶，蛋白激酶（Tyr），受体/通道/细胞表面蛋白， RNA结合蛋白，转录调节物，肿瘤抑制蛋白，泛素偶联系统蛋白和功能未知的蛋白。

公开(公告)号：US20090258436A1

公开(公告)日：2009-10-15

申请号：US12309310

申请日：2007-07-13

申请人： Peter Hornbeck ,  Valerie Goss ,  Ting-Lei Gu ,  Albrecht Moritz ,  Kimberly Lee

发明人： Peter Hornbeck ,  Valerie Goss ,  Ting-Lei Gu ,  Albrecht Moritz ,  Kimberly Lee

IPC分类号： G01N33/566 ,  C07K16/18

CPC分类号： C12Q1/485 ,  C07K16/18 ,  C07K16/40 ,  C07K16/44 ,  G01N33/68 ,  G01N33/6842 ,  G01N33/6845 ,  G01N33/6848 ,  G01N33/6872

摘要： The invention discloses novel phosphorylation sites identified in signal transduction proteins and pathways, and provides phosphorylation-site specific antibodies and heavy-isotope labeled peptides (AQUA peptides) for the selective detection and quantification of these phosphorylated sites/proteins, as well as methods of using the reagents for such purpose. Among the phosphorylation sites identified are sites occurring in the following protein types: adaptor/scaffold proteins, adhesion/extracellular matrix protein, apoptosis proteins, calcium binding proteins, cell cycle regulation proteins, chaperone proteins, chromatin, DNA binding/repair/replication proteins, cytoskeletal proteins, endoplasmic reticulum or golgi proteins, enzyme proteins, G/regulator proteins, inhibitor proteins, motor/contractile proteins, phosphatase, protease, Ser/Thr protein kinases, Protein kinase (Tyr)s, receptor/channel/cell surface proteins, RNA binding proteins, transcriptional regulators, tumor suppressor proteins, ubiquitan conjugating system proteins and proteins of unknown function.

摘要翻译： 本发明公开了在信号转导蛋白和途径中鉴定的新型磷酸化位点，并提供磷酸化位点特异性抗体和重同位素标记肽（AQUA肽），用于选择性检测和定量这些磷酸化位点/蛋白质，以及使用 用于此目的的试剂。 鉴定的磷酸化位点是发生在以下蛋白质类型中的位点：衔接子/支架蛋白，粘附/细胞外基质蛋白，凋亡蛋白，钙结合蛋白，细胞周期调节蛋白，伴侣蛋白，染色质，DNA结合/修复/复制蛋白， 细胞骨架蛋白，内质网或高尔基体蛋白，酶蛋白，G /调节蛋白，抑制蛋白，运动/收缩蛋白，磷酸酶，蛋白酶，Ser / Thr蛋白激酶，蛋白激酶（Tyr），受体/通道/细胞表面蛋白， RNA结合蛋白，转录调节物，肿瘤抑制蛋白，泛素偶联系统蛋白和功能未知的蛋白。

公开(公告)号：US20090142777A1

公开(公告)日：2009-06-04

申请号：US11973019

申请日：2007-10-05

申请人： Valerie Goss ,  Albrecht Moritz ,  Ting-Lei Gu ,  Kimberly Lee ,  Roberto Polakiewicz

发明人： Valerie Goss ,  Albrecht Moritz ,  Ting-Lei Gu ,  Kimberly Lee ,  Roberto Polakiewicz

IPC分类号： G01N33/573 ,  G01N33/566 ,  C07K16/18 ,  C07K14/00 ,  C12N5/06

CPC分类号： C07K16/3061 ,  C07K16/40

摘要： The invention discloses 424 novel phosphorylation sites identified in signal transduction proteins and pathways underlying human Leukemia, and provides phosphorylation-site specific antibodies and heavy-isotope labeled peptides (AQUA peptides) for the selective detection and quantification of these phosphorylated sites/proteins, as well as methods of using the reagents for such purpose. Among the phosphorylation sites identified are sites occurring in the following protein types: Adaptor/Scaffold proteins, Cytoskeletal proteins, Cellular Metabolism enzymes, G Protein/GTPase Activating/Guanine Nucleotide Exchange Factor proteins, Immunoglobulin Superfamily proteins, Inhibitor proteins, Lipid Kinases, Nuclear DNA Repair/RNA Binding/Transcription proteins, Serine/Threonine Protein Kinases, Tyrosine Kinases, Protein Phosphatases, and Translation/Transporter proteins.

摘要翻译： 本发明公开了在信号转导蛋白中鉴定的424个新的磷酸化位点和人类白血病的途径，并提供磷酸化位点特异性抗体和重同位素标记肽（AQUA肽），用于选择性检测和定量这些磷酸化位点/蛋白质 作为使用试剂用于此目的的方法。 所鉴定的磷酸化位点是以下蛋白质类型的位点：适配器/支架蛋白，细胞骨架蛋白，细胞代谢酶，G蛋白/ GTP酶激活/鸟嘌呤核苷酸交换因子蛋白，免疫球蛋白超家族蛋白，抑制蛋白，脂质激酶，核DNA 修复/ RNA结合/转录蛋白，丝氨酸/苏氨酸蛋白激酶，酪氨酸激酶，蛋白磷酸酶和翻译/转运蛋白。

公开(公告)号：US07973134B2

公开(公告)日：2011-07-05

申请号：US11503096

申请日：2006-08-11

申请人： Albrecht Moritz ,  Kimberly Lee ,  John Rush ,  Roberto Polakiewicz

发明人： Albrecht Moritz ,  Kimberly Lee ,  John Rush ,  Roberto Polakiewicz

IPC分类号： C07K16/00 ,  C07K16/18

CPC分类号： G01N33/6842 ,  C07K16/44

摘要： The invention discloses 211 novel phosphorylation sites identified in signal transduction proteins and pathways underlying Anaplastic Large Cell Lymphoma (ALCL) involving the ALK-NPM translocation/fusion, and provides phosphorylation-site specific antibodies and heavy-isotope labeled peptides (AQUA peptides) for the selective detection and quantification of these phosphorylated sites/proteins, as well as methods of using the reagents for such purpose. Among the phosphorylation sites identified are sites occurring in the following protein types: Protein Kinases (including Receptor Tyrosine Kinases), Adaptor/Scaffold Proteins, Cellular Metabolism or Miscellaneous Enzymes, Oxidoreductases, Transcription Factors, Cytoskeletal Proteins, Translation Initiation Complexes, RNA Binding Proteins, Proteases, Acetyltransferases, G protein regulators/GTPases, Helicases, Apoptosis/Cell Cycle Regulation proteins, and Hydrolases.

摘要翻译： 本发明公开了在信号转导蛋白中鉴定的211个新的磷酸化位点和涉及ALK-NPM易位/融合的间变性大细胞淋巴瘤（ALCL）的途径，并且为磷酸化位点特异性抗体和重同位素标记的肽（AQUA肽）提供了 这些磷酸化位点/蛋白质的选择性检测和定量，以及使用试剂用于此目的的方法。 鉴定的磷酸化位点是以下蛋白质类型发生的位点：蛋白激酶（包括受体酪氨酸激酶），适配器/支架蛋白，细胞代谢或其他酶，氧化还原酶，转录因子，细胞骨架蛋白，翻译起始复合物，RNA结合蛋白， 蛋白酶，乙酰转移酶，G蛋白调节剂/ GTP酶，Helicases，细胞凋亡/细胞周期调节蛋白和水解酶。

公开(公告)号：US08618260B2

公开(公告)日：2013-12-31

申请号：US12310852

申请日：2007-09-08

申请人： Peter Hornbeck ,  Albrecht Moritz ,  John Rush ,  Steven Gygi

发明人： Peter Hornbeck ,  Albrecht Moritz ,  John Rush ,  Steven Gygi

IPC分类号： C07K16/00

CPC分类号： G01N33/6842 ,  C07K16/44 ,  G01N2440/14

摘要： The invention discloses 155 novel phosphorylation sites identified in carcinoma and leukemia, peptides (including AQUA peptides) comprising a phosphorylation site of the invention, antibodies specifically bind to a novel phosphorylation site of the invention, and diagnostic and therapeutic uses of the above.