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：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：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：US20080248490A1

公开(公告)日：2008-10-09

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： C07K16/18 ,  G01N33/53

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，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：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：US20090325189A1

公开(公告)日：2009-12-31

申请号：US12311102

申请日：2007-09-18

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

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

IPC分类号： G01N33/53 ,  C07K16/18

CPC分类号： C07K16/44

摘要： The invention discloses 443 novel phosphorylation sites identified in 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.

摘要翻译： 本发明公开了在白血病中鉴定的443个新的磷酸化位点，包含本发明的磷酸化位点的肽（包括AQUA肽），特异性结合本发明的新的磷酸化位点的抗体，以及上述的诊断和治疗用途。

公开(公告)号：US20110104820A1

公开(公告)日：2011-05-05

申请号：US12902261

申请日：2010-10-12

申请人： John Edward Rush, II ,  Ting-Lei Gu ,  Valerie Goss ,  Anthony Possemato

发明人： John Edward Rush, II ,  Ting-Lei Gu ,  Valerie Goss ,  Anthony Possemato

IPC分类号： G01N33/566 ,  C07K16/00

CPC分类号： C07K16/44 ,  C07K2317/34 ,  G01N33/574 ,  G01N33/6842

摘要： The invention discloses 94 novel phosphorylation sites identified in carcinoma and leukemia, peptides (including AQUA peptides) comprising a phosphorylation site of the invention, antibodies that specifically bind to a novel phosphorylation site of the invention, and diagnostic and therapeutic uses of the above.

摘要翻译： 本发明公开了在癌和白血病中鉴定的94个新的磷酸化位点，包含本发明的磷酸化位点的肽（包括AQUA肽），特异性结合本发明的新的磷酸化位点的抗体以及上述的诊断和治疗用途。

公开(公告)号：US20090285796A1

公开(公告)日：2009-11-19

申请号：US12161512

申请日：2007-01-19

申请人： Valerie Goss ,  Ting-lei Gu ,  Roberto Polakiewicz ,  Brian Druker ,  Denise Walters

发明人： Valerie Goss ,  Ting-lei Gu ,  Roberto Polakiewicz ,  Brian Druker ,  Denise Walters

IPC分类号： A61K39/395 ,  C07H21/04 ,  C07K14/00 ,  C12N15/63 ,  C12N5/10 ,  C12N9/12 ,  C07K16/00 ,  C12Q1/68 ,  G01N33/53 ,  A61K31/7088 ,  A61P35/02

CPC分类号： C12N9/1205 ,  C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/136

摘要： In accordance with the invention, a novel activating mutation (alanine 572 to valine) in JAK3 kinase has been discovered in human acute myelogenous leukemia (AML). The mutant JAK3 kinase was confirmed to drive the proliferation and survival of acute megakaryoblastic leukemia (AML-M7). The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant JAK3 kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the mutant polypeptides. The disclosed identification of this new mutant protein and enables new methods for determining the presence of mutant JAK3 kinase polypeptides in a biological sample, methods for screening for compounds that inhibit the mutant proteins, and methods for inhibiting the progression of a cancer characterized by the mutant polynucleotides or polypeptides, which are also provided by the invention.

摘要翻译： 根据本发明，已经在人类急性骨髓性白血病（AML）中发现JAK3激酶中的新的活化突变（丙氨酸572至缬氨酸）。 证实突变型JAK3激酶能够驱动急性巨核细胞白血病（AML-M7）的增殖和存活。 因此，本发明部分地提供分离的多核苷酸和编码所公开的突变体JAK3激酶多肽的载体，用于检测其的探针，分离的突变多肽，重组多肽和用于检测突变体多肽的试剂。 所公开的这种新的突变蛋白的鉴定并且使得能够确定生物样品中突变体JAK3激酶多肽的存在的新方法，用于筛选抑制突变蛋白质的化合物的方法，以及用于抑制突变体特征的癌症进展的方法 多核苷酸或多肽，其也由本发明提供。