WO2006113050A4 - Reagents for the detection of protein phosphorylation in carcinoma signaling pathways - Google Patents
Reagents for the detection of protein phosphorylation in carcinoma signaling pathways Download PDFInfo
- Publication number
- WO2006113050A4 WO2006113050A4 PCT/US2006/010868 US2006010868W WO2006113050A4 WO 2006113050 A4 WO2006113050 A4 WO 2006113050A4 US 2006010868 W US2006010868 W US 2006010868W WO 2006113050 A4 WO2006113050 A4 WO 2006113050A4
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- WO
- WIPO (PCT)
- Prior art keywords
- phosphorylated
- antibody
- column
- tyrosine
- protein
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57484—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
- G01N33/57496—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites involving intracellular compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4748—Tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/44—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material not provided for elsewhere, e.g. haptens, metals, DNA, RNA, amino acids
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- Cell Biology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Urology & Nephrology (AREA)
- Biophysics (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Food Science & Technology (AREA)
- Analytical Chemistry (AREA)
- Physics & Mathematics (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Oncology (AREA)
- Hospice & Palliative Care (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Peptides Or Proteins (AREA)
Abstract
The invention discloses (214) novel phosphorylation sites identified in signal transduction proteins and pathways underlying human carcinoma, 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, Cytoskeleton proteins, GTP Signaling proteins, Kinases, Metabolism proteins, Phosphatases/Phospho- diesterases/ Proteases, Receptor proteins, RNA Processing proteins, Transcription proteins, Translation proteins, Transporter proteins, and Ubitquitin proteins, as well as other protein types.
Claims
82
AMENDED CLAIMS [Received by the International Bureau on 22 DEC 2008 (22.12.2008)]
49. A method selected from the group consisting of:
5 (a) a method for detecting a human carcinoma-related signaling protein selected from Rows 139, 123, 93, 97, 45, 94, 122 and 124 in Column A of Table 1, wherein said human carcinoma-related signaling protein is phosphorylated at the tyrosine listed in corresponding Column D of Table 1, comprised within the phosphorylatable peptide sequence listed in corresponding Column E of Table 1 (SEQ ID NOs: 138,0 122, 92, 9644, 93, 121 and 123), comprising the step of adding an isolated phosphorylation-specific antibody according to claim 14, to a sample comprising said human carcinoma-related signaling protein under conditions that permit the binding of said antibody to said human carcinoma-related signaling protein, and detecting bound antibody; 5 (b) a method for quantifying the amount of a human carcinoma-related signaling protein listed in Rows 139, 123, 93, 97, 45, 94, 122 and 124 in Column A of Table 1 that is phosphorylated at the corresponding tyrosine listed in Column D of Table 1 , comprised within the phosphorylatable peptide sequence listed in corresponding Column E of Table 1 (SEQ ID NOs: 138, 122, 92, 96 44, 93, 121 and 123), in a 0 sample using a heavy-isotope labeled peptide (AQUA ™ peptide), said labeled peptide comprising a phosphorylated tyrosine at said corresponding tyrosine listed Column D of Table 1, comprised within the phosphorylatable peptide sequence listed in corresponding Column E of Table 1 (SEQ ID NOs: 138, 122, 92, 9644, 93, 121 and 123) as an internal standard; and 5 (c) a method comprising step (a) followed by step (b).
50. The method of claim 49, wherein said isolated phosphorylation-specific antibody is capable of specifically binding PDGFRa only when phosphorylated at Y849, comprised within the phosphorylatable peptide sequence listed in Column E, Row 139, of Table 1 (SEQ ID NO: 138), wherein said antibody does not bind said 0 protein when not phosphorylated at said tyrosine.
51. The method of claim 49, wherein said isolated phosphorylation-specific
83 antibody is capable of specifically binding PDGFRa only when not phosphorylated at Y849, comprised within the phosphorylatable peptide sequence listed in Column E, Row 139, of Table 1 (SEQ ID NO: 138), wherein said antibody does not bind said protein when phosphorylated at said tyrosine.
52. The method of claim 49, wherein said isolated phosphorylation-specific antibody is capable of specifically binding LYN only when phosphorylated at Y 193, comprised within the phosphorylatable peptide sequence listed in Column E, Row 123, of Table 1 (SEQ ID NO: 122), wherein said antibody does not bind said protein when not phosphorylated at said tyrosine.
53. The method of claim 49, wherein said isolated phosphorylation-specific antibody is capable of specifically binding LYN only when not phosphorylated at Yl 93, comprised within the phosphorylatable peptide sequence listed in Column E, Row 123, of Table 1 (SEQ ID NO: 122), wherein said antibody does not bind said protein when phosphorylated at said tyrosine.
54. The method of claim 49, wherein said isolated phosphorylation-specific antibody is capable of specifically binding Cdk2, only when phosphorylated at Y 19, comprised within the phosphoiylatable peptide sequence listed in Column E, Row 93, of Table 1 (SEQ ID NO: 92), wherein said antibody does not bind said protein when not phosphorylated at said tyrosine.
55. The method of claim 49, wherein said isolated phosphorylation-specific antibody is capable of specifically binding Cdk2 only when not phosphorylated at Y 19, comprised within the phosphoiylatable peptide sequence listed in Column E, Row 93, of Table 1 (SEQ ID NO: 92), wherein said antibody does not bind said protein when phosphorylated at said tyrosine.
56. The method of claim 49, wherein said isolated phosphorylation-specific antibody is capable of specifically binding DYRK4 only when phosphorylated at Y264, comprised within the phosphorylatable peptide sequence listed in Column E, Row 97, of Table 1 (SEQ ID NO: 96), wherein said antibody does not bind said protein when not phosphorylated at said tyrosine.
84
57. The method of claim 49, wherein said isolated phosphorylation-specific antibody is capable of specifically binding DYK4 only when not phosphorylated at Y264, comprised within the phosphorylatable peptide sequence listed in Column E, Row 97, of Table 1 (SEQ ID NO: 96), wherein said antibody does not bind said protein when phosphorylated at said tyrosine.
58. The method of claim 49, wherein said isolated phosphorylation-specific antibody is capable of specifically binding actin, beta only when phosphorylated at Y 169, comprised within the phosphorylatable peptide sequence listed in Column E, Row 45, of Table 1 (SEQ ID NO: 44), wherein said antibody does not bind said protein when not phosphorylated at said tyrosine.
59. The method of claim 49, wherein said isolated phosphorylation-specific antibody is capable of specifically binding actin, beta only when not phosphorylated at Y 169, comprised within the phosphorylatable peptide sequence listed in Column E, Row 45, of Table 1 (SEQ ID NO: 44), wherein said antibody does not bind said protein when phosphorylated at said tyrosine.
60. The method of claim 49, wherein said isolated phosphorylation-specific antibody is capable of specifically binding Cdk2 only when phosphorylated at Yl 5, comprised within the phosphorylatable peptide sequence listed in Column E, Row 94, of Table I (SEQ ID NO: 93), wherein said antibody does not bind said protein when not phosphorylated at said tyrosine.
61. The method of claim 49, wherein said isolated phosphorylation-specific antibody is capable of specifically binding Cdk2 only when not phosphorylated at Yl 5, comprised within the phosphorylatable peptide sequence listed in Column E, Row 94, of Table 1 (SEQ ID NO: 93), wherein said antibody does not bind said protein when phosphorylated at said tyrosine.
62. The method of claim 49, wherein said isolated phosphorylation-specific antibody is capable of specifically binding Fyn only when phosphorylated at Y439, comprised within the phosphorylatable peptide sequence listed in Column E, Row 122, of Table 1 (SEQ ID NO: 121), wherein said antibody does not bind said protein
85 when not phosphorylated at said tyrosine.
63. The method of claim 49, wherein said isolated phosphorylation-specifϊc antibody is capable of specifically binding Fyn only when not phosphorylated at Y439, comprised within the phosphorylatable peptide sequence listed in Column E, Row 122, of Table 1 (SEQ ID NO: 121), wherein said antibody does not bind said protein when phosphorylated at said tyrosine.
64. The method of claim 49, wherein said isolated phosphorylation-specific antibody is capable of specifically binding AxI only when phosphorylated at Y696, comprised within the phosphorylatable peptide sequence listed in Column E, Row 124, of Table 1 (SEQ ID NO: 123), wherein said antibody does not bind said protein when not phosphorylated at said tyrosine.
65. The method of claim 49, wherein said isolated phosphorylation-specific antibody is capable of specifically binding AxI only when not phosphorylated at Y696, comprised within the phosphorylatable peptide sequence listed in Column E, Row 124, of Table 1 (SEQ ID NO: 123), wherein said antibody does not bind said protein when phosphorylated at said tyrosine.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP06739581A EP1872134A4 (en) | 2005-04-12 | 2006-03-24 | REAGENTS FOR DETECTION OF PHOSPHORYLATION OF PROTEINS IN THE CARCINOMA SIGNALING PATHWAY |
| US12/985,879 US20110105732A1 (en) | 2005-04-12 | 2011-01-06 | Reagents for the Detection of Protein Phosphorylation in Carcinoma Signaling Pathways |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US67044705P | 2005-04-12 | 2005-04-12 | |
| US60/670,447 | 2005-04-12 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US67044705P Continuation | 2005-04-12 | 2005-04-12 |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US11/974,480 Continuation US20090099340A1 (en) | 2005-04-12 | 2007-10-12 | Reagents for the detection of protein phosphorylation in carcinoma signaling pathways |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| WO2006113050A2 WO2006113050A2 (en) | 2006-10-26 |
| WO2006113050A8 WO2006113050A8 (en) | 2007-12-27 |
| WO2006113050A3 WO2006113050A3 (en) | 2008-12-24 |
| WO2006113050A4 true WO2006113050A4 (en) | 2009-03-26 |
Family
ID=37115632
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US2006/010868 Ceased WO2006113050A2 (en) | 2005-04-12 | 2006-03-24 | Reagents for the detection of protein phosphorylation in carcinoma signaling pathways |
Country Status (2)
| Country | Link |
|---|---|
| EP (1) | EP1872134A4 (en) |
| WO (1) | WO2006113050A2 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8242083B2 (en) * | 2008-06-23 | 2012-08-14 | Perkinelmer Health Sciences, Inc. | Kinase substrates |
| CN111116734A (en) * | 2019-12-23 | 2020-05-08 | 维塔恩(广州)医药有限公司 | Tumor-associated gene c-kit mutation-associated antigen short peptide and application thereof |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0640102B1 (en) * | 1992-04-10 | 2006-08-09 | Dana-Farber Cancer Institute, Inc. | Activation-state-specific phosphoprotein immunodetection |
| WO2002081638A2 (en) * | 2001-04-06 | 2002-10-17 | Origene Technologies, Inc | Prostate cancer expression profiles |
| US7335467B2 (en) * | 2001-05-15 | 2008-02-26 | Ludwig Institute For Cancer Research | Breast cancer antigens |
-
2006
- 2006-03-24 EP EP06739581A patent/EP1872134A4/en not_active Withdrawn
- 2006-03-24 WO PCT/US2006/010868 patent/WO2006113050A2/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| WO2006113050A8 (en) | 2007-12-27 |
| EP1872134A2 (en) | 2008-01-02 |
| WO2006113050A3 (en) | 2008-12-24 |
| WO2006113050A2 (en) | 2006-10-26 |
| EP1872134A4 (en) | 2010-09-01 |
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