摘要:
A meg-CSF/thrombopoietin-like protein that is present in plasma of irradiated pigs has been purified. This protein, the porcine Mpl ligand polypeptide (ML), binds to and activates the c-Mpl receptor protein, a member of the cytokine receptor superfamily. The isolated Mpl ligand stimulates both megakaryocytopoiesis and thrombopoiesis.
摘要:
Novel vertebrate homologues of Smoothened, including human and rat Smoothened, are provided. Compositions including vertebrate Smoothened chimeras, nucleic acid encoding vertebrate Smoothened, and antibodies to vertebrate Smoothened, are also provided.
摘要:
The emergence of mutations in tyrosine kinases following treatment of cancer patients with molecular-targeted therapy represents a major mechanism of acquired drug resistance. Here, we describe a mutation in the serpentine receptor, Smoothened (SMO), which results in resistance to a Hedgehog (Hh) pathway inhibitor in medulloblastoma. A single amino acid substitution in a conserved aspartic acid residue of SMO maintains Hh signaling, but results in the inability of the Hh pathway inhibitor, GDC-0449, to bind SMO and suppress the pathway. This mutation was not only acquired in a GDC-0449-resistant mouse model of medulloblastoma, but was identified in a Medulloblastoma patient following relapse on GDC-0449. The invention provides screening methods to detect SMO mutations and methods to screen for drugs that specifically modulate mutant SMO exhibiting drug resistance.
摘要:
The present invention relates to transgenic animals, as well as compositions and methods relating to the characterization of gene function. Specifically, the present invention provides transgenic mice comprising disruptions in PRO224, PRO9783, PRO1108, PRO34000, PRO240, PRO943, hu A33, PRO230, PRO178, PRO1199, PRO4333, PRO1336, PRO19598, PRO1083, hu TRPM2 or PRO1801 genes.Such in vivo studies and characterizations may provide valuable identification and discovery of therapeutics and/or treatments useful in the prevention, amelioration or correction of diseases or dysfunctions associated with gene disruptions such as neurological disorders; cardiovascular, endothelial or angiogenic disorders; eye abnormalities; immunological disorders; oncological disorders; bone metabolic abnormalities or disorders; lipid metabolic disorders; or developmental abnormalities.
摘要:
The emergence of mutations in tyrosine kinases following treatment of cancer patients with molecular-targeted therapy represents a major mechanism of acquired drug resistance. Here, we describe a mutation in the serpentine receptor, Smoothened (SMO), which results in resistance to a Hedgehog (Hh) pathway inhibitor in medulloblastoma. A single amino acid substitution in a conserved glutamic acid residue of SMO maintains Hh signaling, but results in the inability of the Hh pathway inhibitor, GDC-0449, to bind SMO and suppress the pathway. The invention provides screening methods to detect SMO mutations and methods to screen for drugs that specifically modulate mutant SMO exhibiting drug resistance.
摘要:
The present invention relates to methods for the treatment and diagnosis of immune related diseases, including those mediated by cytokines released primarily either Th1 or Th2 cells in response to antigenic stimulation. The present invention further relates to methods for biasing the differentiation of T-cells in either the Th1 subtype or the Th2 subtype, based on the relative expression levels of the gene TCCR, and its agonists or antagonists. The present invention further relates to a method of diagnosing Th1- and Th2-mediated diseases.
摘要:
The present invention relates to transgenic animals, as well as compositions and methods relating to the characterization of gene function. Specifically, the present invention provides transgenic mice comprising disruptions in PRO226, PRO257, PRO268, PRO290, PRO36006, PRO363, PRO365, PRO382, PRO444, PRO705, PRO1071, PRO1125, PRO1134, PRO1155, PRO1281, PRO1343, PRO1379, PRO1380, PRO1387, PRO1419, PRO1433, PRO1474, PRO1550, PRO1571, PRO1572, PRO1759, PRO1904, PRO35193, PRO4341, PRO4348, PRO4369, PRO4381, PRO4407, PRO4425, PRO4985, PRO4989, PRO5737, PRO5800, PRO5993, PRO6017, PRO7174, PRO9744, PRO9821, PRO9852, PRO9873, PRO10196, PRO34778, PRO20233, PRO21956, PRO57290, PRO38465, PRO38683 or PRO85161 genes. Such in vivo studies and characterizations may provide valuable identification and discovery of therapeutics and/or treatments useful in the prevention, amelioration or correction of diseases or dysfunctions associated with gene disruptions such as neurological disorders; cardiovascular, endothelial or angiogenic disorders; eye abnormalities; immunological disorders; oncological disorders; bone metabolic abnormalities or disorders; lipid metabolic disorders; or developmental abnormalities.
摘要:
The present invention is directed to novel polypeptides having homology to a polypeptide suppressor of the Drosophila melanogaster fused protein and to nucleic acid molecules encoding those polypeptides. Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, antibodies which bind to the polypeptides of the present invention and to methods for producing the polypeptides of the present invention.
摘要:
The present invention relates to nucleotide sequences, including expressed sequence tags (ESTs), oligonucleotide probes, polypeptides, antibodies, vectors and host cells expressing, immunoadhesins, agonists and antagonists to patched-2.