Abstract: The invention discloses 168 novel phosphorylation sites identified in signal transduction proteins and pathways downstream of, and including, EGFR kinase, 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: Actin Binding proteins, Adaptor/Scaffold proteins, Calcium-Binding Proteins, Cell Cycle Regulation proteins, Cytoskeletal proteins, DNA Binding and Replication Proteins, GTPase Activating proteins, Guanine Nucleotide Exchange Factor proteins, Lipid Kinases, Receptor Tyrosine Kinases, Receptor Tyrosine Kinase ligands, Protein Kinases, Receptor and Protein Phosphatases, Transcription Factor proteins, Tumor Suppressor proteins, and Vesicle proteins.

Abstract: The invention relates to antibody reagents that specifically bind to peptides carrying a ubiquitin remnant from a digested or chemically treated biological sample. The reagents allow the technician to identify ubiquitinated polypeptides as well as the sites of ubiquitination on them. The reagents are preferably employed in proteomic analysis using mass spectrometry. The antibody reagents specifically bind to the remnant of ubiquitin (i.e., a diglycine modified epsilon amine of lysine) left on a peptide which as been generated by digesting or chemically treating ubiquitinated proteins. The inventive antibody reagents' affinity to the ubiquitin remnant does not depend on the remaining amino acid sequences flanking the modified (i.e., ubiquitinated) lysine, i.e., they are context independent.

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.

Abstract: The invention discloses a previously unidentified subset of mammalian non-small cell lung carcinomas (NSCLC) in which platelet-derived growth factor receptor alpha (PDGFR?) is expressed and is driving the disease, and provides methods for identifying a mammalian NSCLC tumor that belongs to a subset of NSCLC tumors in which PDGFR? is expressed, and for identifying a NSCLC tumor that is likely to respond to a PDGFR?-inhibiting therapeutic. The invention also provides methods for inhibiting the progression of a mammalian NSCLC tumor in which PDGFR? is expressed, and for determining whether a compound inhibits the progression of a PDGFR?-expressing mammalian NSCLC tumor.

Abstract: The invention discloses 726 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.

Abstract: The invention discloses 990 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.

Abstract: In accordance with the invention, novel gene deletions and translocations involving chromosome 2 resulting in fusion proteins combining part of Anaplastic Lymphoma Kinase (ALK) kinase with part of a secondary protein have now been identified in human solid tumors, e.g. non-small cell lung carcinoma (NSCLC). Secondary proteins include Echinoderm Microtubule-Associated Protein-Like 4 (EML-4) and TRK-Fusion Gene (TFG). The EML4-ALK fusion protein, which retains ALK tyrosine kinase activity, was confirmed to drive the proliferation and survival of NSCLC characterized by this mutation. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant ALK kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides.

Abstract: The invention discloses 137 novel phosphorylation sites identified in insulin signaling pathways, 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.

Abstract: In accordance with the invention, novel gene deletions and translocations involving chromosome 2 resulting in fusion proteins combining part of Anaplastic Lymphoma Kinase (ALK) kinase with part of a secondary protein have now been identified in human solid tumors, e.g. non-small cell lung carcinoma (NSCLC). Secondary proteins include Echinoderm Microtubule-Associated Protein-Like 4 (EML-4) and TRK-Fusion Gene (TFG). The EML4-ALK fusion protein, which retains ALK tyrosine kinase activity, was confirmed to drive the proliferation and survival of NSCLC characterized by this mutation. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant ALK kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides.

Abstract: In accordance with the invention, a novel gene translocation, (4p15, 6q22), in human non-small cell lung carcinoma (NSCLC) that results in a fusion proteins combining part of Sodium-dependent Phosphate Transporter Isoform NaPi-3h protein (SLC34A2) with Proto-oncogene Tyrosine Protein Kinase ROS Precursor (ROS) kinase has now been identified. The SLC34A2-ROS fusion protein is anticipated to drive the proliferation and survival of a subgroup of NSCLC tumors. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant ROS kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides.

Abstract: The invention discloses 168 novel phosphorylation sites identified in signal transduction proteins and pathways downstream of, and including, EGFR kinase, 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: Actin Binding proteins, Adaptor/Scaffold proteins, Calcium-Binding Proteins, Cell Cycle Regulation proteins, Cytoskeletal proteins, DNA Binding and Replication Proteins, GTPase Activating proteins, Guanine Nucleotide Exchange Factor proteins, Lipid Kinases, Receptor Tyrosine Kinases, Receptor Tyrosine Kinase ligands, Protein Kinases, Receptor and Protein Phosphatases, Transcription Factor proteins, Tumor Suppressor proteins, and Vesicle proteins.

Abstract: In accordance with the invention, novel gene deletions and translocations involving chromosome 2 resulting in fusion proteins combining part of Anaplastic Lymphoma Kinase (ALK) kinase with part of a secondary protein have now been identified in human solid tumors, e.g. non-small cell lung carcinoma (NSCLC). Secondary proteins include Echinoderm Microtubule-Associated Protein-Like 4 (EML-4) and TRK-Fusion Gene (TFG). The EML4-ALK fusion protein, which retains ALK tyrosine kinase activity, was confirmed to drive the proliferation and survival of NSCLC characterized by this mutation. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant ALK kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides.

Abstract: In accordance with the invention, a novel gene translocation, (5q32, 6q22), in human non-small cell lung carcinoma (NSCLC) that results in a fusion proteins combining part of CD74 with Proto-oncogene Tyrosine Protein Kinase ROS Precursor (ROS) kinase has now been identified. The CD74-ROS fusion protein is anticipated to drive the proliferation and survival of a subgroup of NSCLC tumors. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant ROS kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides.

Abstract: The invention discloses nearly 219 novel phosphorylation sites identified in signal transduction proteins and pathways underlying Anaplastic Large Cell Lymphoma (ALCL) involving the NPM-ALK 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.

Abstract: The invention discloses 461 novel phosphorylation sites identified in basophilic Ser/Thr kinase signaling pathways, 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.

Abstract: The invention discloses nearly 443 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: Protein kinases (including Serine/Threonine dual specificity, and Tyrosine kinases), Adaptor/Scaffold proteins, Transcription factors, Phospoatases, Tumor supressors, Ubiquitin conjugating system proteins, Translation initiation complex proteins, RNA binding proteins, Apoptosis proteins, Adhesion proteins, G protein regulators/GTPase activating protein/Guanine nucleotide exchange factor proteins, and DNA binding/replication/repair proteins, as well as other protein types.

Abstract: In accordance with the invention, a novel gene translocation, (4p15, 6q22), in human non-small cell lung carcinoma (NSCLC) that results in fusion proteins combining part of Sodium-dependent Phosphate Transporter Isoform NaPi-3b protein (SLC34A2) with Proto-oncogene Tyrosine Protein Kinase ROS Precursor (ROS) kinase has now been identified. The SLC34A2-ROS fusion proteins are anticipated to drive the proliferation and survival of cancer cells, and particularly drive the proliferation and survival of a subgroup of NSCLC tumor cells. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant ROS kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides.

Abstract: The invention discloses 347 novel phosphorylation sites identified in carcinoma, 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.

Abstract: The invention discloses 349 novel phosphorylation sites identified in carcinoma, 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.

Abstract: The invention discloses 351 novel phosphorylation sites identified in carcinoma, 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.