Abstract: This invention relates to novel human polynucleotides and variants thereof, their encoded polypeptides and variants thereof, to genes corresponding to these polynucleotides and to proteins expressed by the genes. The invention also relates to diagnostic and therapeutic agents employing such novel human polynucleotides, their corresponding genes or gene products, e.g., these genes and proteins, including probes, antisense constructs, and antibodies.

Abstract: The invention is generally directed to compositions and methods for affecting signal transduction using the casein kinase I (CKI) gene or gene product. The invention is more specifically directed to affecting the Wnt signal pathway using the CKI gene or gene product. The invention is particularly directed to using the CKI gene or gene product to treat and diagnose cancer, particularly breast and colon cancer. CKI&egr; is the preferred species. The field of the invention is compositions and methods for modulating signal transduction using the (CKI) gene or gene products and variants thereof. The invention is more specifically directed to modulating the Wnt signal pathway using the CKI gene or gene product. The invention is particularly directed to using the CKI gene or gene product to treat and diagnose disorders mediated by the Wnt signal pathway, especially hyperproliferative disorders, particularly breast and colon cancer.

Abstract: A DNA sequence encoding human platelet-derived growth factor receptor (hPDGF-R) has now been isolated and sequenced. An expression construct comprising the sequence encodes a receptor that can be secreted or incorporated into the membrane of a mammalian cell. The incorporated receptor is functionally equivalent to the wild-type receptor, conferring a PDGF-sensitive mitogenic response on cells lacking the receptor. The construct can be used for enhancing PDGF response of cells, determining the regions involved in transducing the signal in response to PDGF binding, providing mutated analogs and evaluating drugs for their physiologic activity.

Abstract: The present invention generally relates to novel GRB2 associating proteins and nucleic acids which encode these protein. In particular, these novel proteins possess inositol polyphosphate 5-phosphatase and phosphatidylinositol 5-phosphatase activities, important in growth factor mediated signal transduction. As such, the proteins, nucleic acids encoding the proteins, cells capable of expressing these nucleic acids and antibodies specific for these proteins will find a variety of uses in a variety of screening, therapeutic and other applications.

Abstract: The present invention generally provides peptides that comprise a recognition sequence motif for phosphotyrosine binding proteins. In particular, the present invention provides peptides which comprise a core sequence of amino acids, and analogs thereof, which are recognized and bound by the PTB (phosphotyrosine binding) domain. Also provided are methods of using the peptides of the invention in diagnostic, screening and therapeutic applications.

Abstract: The present invention generally relates to novel GRB2 associating proteins and nucleic acids which encode these protein. In particular, these novel proteins possess inositol polyphosphate 5-phosphatase and phosphatidylinositol 5-phosphatase activities, important in growth factor mediated signal transduction. As such, the proteins, nucleic acids encoding the proteins, cells capable of expressing these nucleic acids and antibodies specific for these proteins will find a variety of uses in a variety of screening, therapeutic and other applications.

Abstract: Isolated nucleic acid molecules comprising polynucleotide having sequences that encode human and Drosophila PAR-1 kinases. Also provided are proteins and polypeptides encoded by the nucleic acid molecules, methods of modulating PAR-1 expression and function, and methods of modulating the Wnt signaling pathway.

Abstract: A human gene encoding a novel cyclin-dependent kinase termed hPFTAIRE and its expression products can be used to provide reagents and methods for detecting migrating or metastasizing cells. Compositions and methods for treating proliferative disorders and neoplasia are also provided.

Abstract: Secreted proteins can be identified using a method which exploits the ability of microsomes to modify proteins post-translationally. Nineteen human secreted proteins and full-length cDNA sequences encoding the proteins have been identified using this method. The proteins and cDNA sequences can be used, inter alia, for targeting other proteins to the membrane or extracellular milieu.

Abstract: The invention provides materials and methods for determining the metastatic potential of a cell and for identifying cancerous cells by determining the presence or absence of one or more expression products of at least one gene that is differentially expressed between normal cells, nonmetastatic cells, cells of low metastatic potential, and cells of high metastatic potential.

Abstract: Two novel proteins that interact with mammalian Dishevelled protein, and the corresponding polynucleotide sequences encoding the proteins, are disclosed. The proteins are referred to as mNkd and DAP 1A. mNkd is expressed at a higher level in mammalian lung tissues than in other mammalian tissues. mNkd inhibits Wnt signaling, and is an activator of the JNK pathway.

Abstract: A fibroblast growth factor (FGF) receptor including a basic fibroblast growth factor receptor has been purified. Various forms have been identified including soluble forms lacking any transmembrane segment. DNA sequences encoding full-length fibroblast growth factor receptors and polypeptides comprising a portion of an FGF-R ligand-binding domain have been isolated and sequenced. These DNAs include DNAs encoding for a basic FGF-R and a human FGF-R and are operably linked to control sequences and expressed in a culture of a compatible host transformed, transfected or electroporated by a cloning vehicle containing the DNA sequence. The invention also comprises antibodies to the receptor, methods of synthesizing the growth factor receptor proteins, methods for providing analogs of the fibroblast growth factor receptors.

Abstract: Inhibitors of KIAA0175 are provided that reduce the expression or biological activities of KIAA0175, p53 and/or p21 in a mammalian cell. KIAA0175 inhibitors include anti-sense molecules, ribozymes, antibodies and antibody fragments, proteins and polypeptides as well as small molecules. KIAA0175 inhibitors find use in compositions and methods for decreasing KIAA0175, p53 and/or p21 gene expression as well as methods for increasing the chemo and/or radiosensitivity of mammalian cells, including tumor cells, methods for decreasing the side effects of cancer therapy and methods for treating neoplastic diseases.

Abstract: The present invention relates to receptors for growth factors, specifically to the fibroblast growth factor receptor (FGF-R). More particularly, it provides various purified fibroblast growth factor receptor proteins, nucleic acids encoding the receptor proteins, methods for the production of purified FGF-R proteins, proteins made by these methods, antibodies against these proteins, diagnostic and therapeutic uses of these various reagents, and methods of detecting a fibroblast growth factor in a sample using the disclosed fibroblast growth factor receptors.

Abstract: A fibroblast growth factor (FGF) receptor including a basic fibroblast growth factor receptor has been purified. Various forms have bee identified including soluble forms lacking any transmembrane segment. DNA sequences encoding full-length fibroblast growth factor receptors and polypeptides comprising a portion of an FGF-R ligand-binding domain have been isolated and sequenced. These DNAs include DNAs encoding for a basic FGF-R and a human FGF-R and are operably linked to control sequences and expressed in a culture of a compatible host transformed, transfected or electroporated by a cloning vehicle containing the DNA sequence. The invention also comprises antibodies to the receptor, methods of synthesizing the growth factor receptor proteins, methods for providing analogs of the fibroblast growth factor receptors.

Abstract: The invention provides a method of producing a constitutively active phosphatidylinositol 3-kinase (PI 3-kinase) comprising the catalytic p110 subunit covalently attached at the N-terminus to the iSH2 region of the regulatory subunit, p85. The invention discloses one form of the constitutively active kinase, p110*, which functions independently of growth factor stimulation. Expression vectors encoding a constitutively active PI 3-kinase and cells containing such expression vectors are provided. The invention also provides methods of using the constitutively active phosphatidylinositol 3-kinase to generate phosphoinositides, to identify cellular target proteins and associating molecules of PI 3-kinase, to screen for inhibitors of PI 3-kinase activity and to treat certain diseases, in particular, proliferative diseases. Kits comprising the constitutively active kinase are also provided.

Abstract: The present invention generally relates to novel GRB2 associating proteins and nucleic acids which encode these protein. In particular, these novel proteins possess inositol polyphosphate 5-phosphatase and phosphatidylinositol 5-phosphatase activities, important in growth factor mediated signal transduction. As such, the proteins, nucleic acids encoding the proteins, cells capable of expressing these nucleic acids and antibodies specific for these proteins will find a variety of uses in a variety of screening, therapeutic and other applications.

Abstract: The present invention generally provides nucleic acids and polypeptides that are phosphatidylinositol 3-kinases, also known as 1-phosphatidylinositol 3-kinases. The nuclecic acids and polypeptides disclosed are derived from Drosophila and mouse. These polypeptides are generally involved in cell signaling cascades which control, e.g., cell cycle progression and intracellular protein sorting. The family of PI3-kinases from which the polypeptides of the invention are derived are generally characterized by their structure as well as their unique substrate specificity.

Abstract: The present invention generally provides peptides that comprise a recognition sequence motif for phosphotyrosine binding proteins. In particular, the present invention provides peptides which comprise a core sequence of amino acids, and analogs thereof, which are recognized and bound by the PTB (phosphotyrosine binding) domain. Also provided are methods of using the peptides of the invention in diagnostic, screening and therapeutic applications.

Abstract: This invention provides nucleic acid sequences for a VEGF receptor promoter, particularly for the Flt-1 promoter, expression vectors and recombinant host cells containing this promoter. It also provides methods for screening for drugs that regulate the transcriptional activity of the VEGF receptor promoter. Methods for endothelial-specific gene expression and treatment of disease, particularly by inhibiting angioigenesis, using novel gene constructs containing the VEGF receptor promoter are also provided. Transgenic animals having heterologous genes linked to the VEGF receptor promoter are also provided.