Abstract: The invention discloses two novel phosphorylation sites in human ATR kinase, serine 428 (Ser428) and serine 2317 (Ser2317) respectively, and provides reagents, including antibodies and AQUA peptides, that selectively bind to and/or detect ATR only when phosphorylated at one or more of these respective sites, but do not bind to ATR when not phosphorylated at these respective sites. Also provided are methods for determining the phosphorylation of ATR kinase in a biological sample, by using a detectable reagent that binds to ATR only when phosphorylated at Ser428 and/or Ser2317. Kits comprising the ATR (Ser428, Ser2317)-specific reagents of the invention are also provided.

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 provides a nucleic acid cassette comprising components in the following structure: A-B-C, wherein “A” is a nucleic acid sequence encoding a light chain of a first antibody (or antigen binding domain thereof), “B” is a nucleic acid sequence encoding a 2A peptide, “C” is a nucleic acid sequence encoding a heavy chain of a second antibody (or antigen binding domain thereof), and “?” is a phosphodiester or phosphorothioate bond. Also provided are methods for making recombinant antibodies using the nucleic acid cassette of the invention, cells and vector comprising the nucleic acid cassette of the invention, and kits for making the nucleic acid cassette of the invention.

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: 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.

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 ten (10) protein markers predictive of cancer resistance or responsiveness to Type III Receptor Tyrosine Kinase (RTK) inhibitors, and provides methods for identifying a cancer that is likely to be resistant to a Type III RTK-inhibiting therapeutic by examining expression and/or activity of one or more of the disclosed biomarkers in a biological sample from the cancer. Methods for identifying a compound that inhibits a cancer resistant to a Type III RTK-inhibiting therapeutic by determining the effect of the compound on one or more of the disclosed marker proteins are also provided.

Abstract: In accordance with the invention, a novel gene translocation in human Hodgkin's lymphoma (HL) that results in a fusion protein combining part of C17ORF61 with Thirty-eight-negative kinase 1 (Tnk1) kinase has now been identified. The TNK1-C17ORF61 fusion protein, which retains TNK1 tyrosine kinase activity, was confirmed to drive the proliferation and survival of Hodgkin's lymphoma (HL) cell line, L-540. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant TNK1 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, 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 present invention relates to methods of classifying cancer cells based on the presence, absence or level of a tyrosine kinase or a phosphorylated tyrosine kinase. The present invention also relates to methods of treating cancer using cancer classification. The present invention further relates to methods of determining the effectiveness of a treatment for cancer using cancer classification.

Abstract: 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.

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 newly-discovered phosphorylation sites in human IRS-1 and IRS-2, serine 1101 (Ser1101) and serine 1149 (Ser1149) respectively, and provides antibodies, both polyclonal and monoclonal, that selectively bind to IRS-1 and/or IRS-2 when phosphorylated at these respective sites, but do not bind to IRS-1 and/or IRS-2 when not phosphorylated at these respective sites. The sites are relevant to insulin-resistance in type 2 diabetes. Also provided are methods for determining the phosphorylation of IRS-1/2 or activity of PKC theta in a biological sample, by using a detectable reagent, such as the disclosed antibodies, that binds to IRS-1/2 only when phosphorylated at Ser1101/Ser1149. Kits comprising the phosphor-IRS-1/2 (Ser1101/1149) antibodies of the invention are also provided.

Abstract: The invention discloses 318 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: 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 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.

Abstract: 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.

Abstract: The present invention is related to a method for producing motif-specific, context-independent antibodies which are specific to at least one modified amino acid residue in the context of variable surrounding amino acid or peptide sequences. The method is particularly useful in producing antibodies which recognize phosphorylated serine, threonine, and tyrosine, or acetylated lysine, as well as other modified amino acids-containing motifs of one or more amino acids.

Abstract: A method is provided for producing motif-specific, context-independent antibodies which recognize a plurality of peptides or proteins within a genome that contain the same motif. The method includes the step of immunizing a host with a degenerate peptide library antigen featuring (i) a fixed target motif containing one or more invariant amino acids including at least one modified amino acid, and (ii) a plurality of degenerate amino adds flanking the motif. Motif-specific, context-independent antibodies produced by the disclosed method are also provided. The method encompasses motifs consisting of a single modified amino acid, as well as short motifs comprising multiple invariant amino acids including one or more modified amino acids, such as all or part of kinase consensus substrate motifs, protein-protein binding motifs, or other cell signaling motifs. Methods of using the antibodies, e.g. for genome-wide profiling, are also provided.