Abstract: Novel class II cytokine receptor polypeptides, polynucleotides encoding the polypeptides, an related compositions and methods are disclosed. Th polypeptides comprise an extracellular domain of a cell-surface receptor that is expressed in pancreas, small intestine, colon and thymus. The polypeptides may be used within methods for detecting ligands that promote the proliferation and/or differentiation of these organs.

Abstract: Disclosed is a method for determining whether a test protein is capable of interacting with a nuclear hormone receptor protein. The method involves: (a) providing a host cell which contains (i) a reporter gene operably linked to a protein binding site; (ii) a first fusion gene which expresses a first fusion protein, the first fusion protein including a nuclear hormone receptor protein covalently bonded to a binding moiety which is capable of specifically binding to the protein binding site; and (iii) a second fusion gene which expresses a second fusion protein, the second fusion protein including the test protein covalently bonded to a weak gene activating moiety; and (b) determining whether the test protein increases expression of the reporter gene as an indication of its ability to interact with the nuclear hormone receptor protein. Such an interaction may be hormone dependent, hormone independnet, or hormone sensitive.

Abstract: The present invention provides purified and isolated polynucleotides encoding IRP (integrin regulatory protein) polypeptides which regulate .beta..sub.2 and .beta..sub.7 integrins and which are contemplated to participate in integrin signaling and/or recycling pathways. Also provided are methods for identifying modulators of IRP activities and methods for identifying other proteins which interact with IRP polypeptides in signaling pathways. Modulators of IRP interactions are contemplated to be useful, for example, in monitoring and treating inflammatory processes involving leukocytes.

Abstract: The present invention provides a method for detecting a biologically active substance that affects intracellular processes mediated through a protein kinase or second messenger, which comprises incubating a cell with a test substance and measuring any change caused by the test substance in the fluorescence of (i) green fluorescent protein (GFP) having a protein kinase recognition site or (ii) GFP that has been modified to contain a second messenger binding domain.

Abstract: The invention relates to a homeoprotein regulator of insulin gene expression having the characteristics of: binding to an element of an insulin gene promoter; being modulated by a Ca.sup.++ -dependent CaM kinase IV; and having homology to a nucleotide sequence encoded by a Hox gene complex. Also included within the invention are DNA sequences encoding the homeoprotein regulators of insulin gene expression, antibodies directed to the homeoprotein regulators of insulin gene expression, and diagnostic and therapeutic materials and utilities for the homeoprotein regulators of insulin gene expression.

Abstract: Oligopeptides having an amino acid sequence corresponding to a receptor's extracellular domain, and having sequence similarity to regulatory peptides from MHC class I antigens, enhance the physiological response of ligand binding to the corresponding receptor. The oligopeptides are used in diagnosis and therapy of diseases that involve inadequate or inappropriate receptor response as well as in the screening of drug candidates that affect surface expression of receptors. Also useful for drug screening is a modified receptor molecule, where the sequence corresponding to the regulatory peptide is modified or deleted.

Abstract: A domain of Bcl-2 that suppresses apoptosis by allowing cell survival permits cell proliferation when mutated. The wild type domain includes amino acid residues 51 to 97 (SEQ ID NO: 13) of Bcl-2. Peptides including the domain and nucleotides encoding the domain are useful in molecular screening of human tumors for the presence of mutations that allow proliferation of cells that were otherwise marked for apoptosis. The peptides are also useful to screen for proteins that play a role in the modulation of cellular proliferation.

Abstract: The present invention is directed to novel VEGF receptor proteins comprising amino acid sequences derived from the vascular endothelial growth factor (VEGF) receptors flt-1, FLT4, and KDR, including the murine homologue to the human KDR receptor FLK-1, wherein said chimeric VEGF receptor proteins bind to VEGF and antagonize the endothelial cell proliferative and angiogenic activity thereof. The present invention is also directed to nucleic acids and expression vectors encoding these chimeric VEGF receptor proteins, host cells harboring such expression vectors, pharmaceutically acceptable compositions comprising such proteins, methods of preparing such proteins and to methods utilizing such proteins for the treatment of conditions associated with undesired vascularization.

Abstract: Novel TNF receptor death domain ("TNF-R1-DD") ligand proteins are disclosed. Polynucleotides encoding the TNF-R1-DD ligand protein are also disclosed, along with vectors, host cells, and methods of making the TNF-R1-DD ligand protein. Pharmaceutical compositions containing the TNF-R1-DD ligand protein, methods of treating inflammatory conditions, and methods of inhibiting TNF-R death domain binding are also disclosed. Methods of identifying inhibitors of TNF-R death domain binding and inhibitors identified by such methods are also disclosed.

Abstract: The invention concerns recombinant antibodies directed to the extracellular domain of the human growth factor receptor c-erbB-2 comprising a light chain variable domain and a heavy chain variable domain of a monoclonal antibody, monoclonal antibodies directed to c-erbB-2 themselves, a method of manufacture of said recombinant antibodies and said monoclonal antibodies, hybridoma cells secreting said monoclonal antibodies, a method of manufacture of said hybridoma cells, DNA coding for the heavy chain variable domain, for the light chain variable domain and for the recombinant antibody, a method of manufacture of said DNA, hybrid vectors suitable for expression of said DNA, host cells transformed with said DNA, and the use of said recombinant antibodies and said monoclonal antibodies in the diagnosis and treatment of tumors.

Abstract: The use of C1-inactivator for the production of a pharmaceutical for the prophylaxis and treatment of capillary leak syndrome (generalized extravasation) and circulator shock (refractory hypotension) in severe burns or scalds, in polytrauma, in operations under conditions of extracorporeal circulation, in the use of cytokines, endogenous mediators, and mediator hybrids and growth factors produced by genetic engineering, or capillary leak syndrome and veno-occlusive disease of the liver in therapeutically or prophylactically indicated bone marrow transplantation is described.

Abstract: The present invention generally relates to novel protein domains which bind to tyrosine-phosphorylated proteins. More particularly, the present invention provides non-SH2 protein domains that bind phosphotyrosine. The present invention also provides various composite polypeptides comprising these domains, such that these composite polypeptides retain the ability to bind tyrosine phosphorylated proteins. It also provides nucleic acids encoding these polypeptides. Typically, these nucleic acids may also comprise a promoter for expression, and a segment encoding fusion peptides on the amino or carboxy terminus of the expressed composite protein. Also included within the present invention are methods of preparing these polypeptides and cells capable of expressing them. Also provided are methods of using these polypeptides in research, diagnostic and therapeutic applications.

Abstract: The present invention provides isolated DNA molecules comprising a DNA segment encoding a glucagon receptor. Also provided are DNA constructs comprising a first DNA segment encoding a glucagon receptor operably linked to additional DNA segments required for the expression of the first DNA segment, as well as host cells containing such DNA constructs.

Abstract: A novel, generally applicable method for producing correctly folded proteins from a mixture of misfolded proteins, e.g. bacterial inclusion-body aggregates. A major new aspect of the method is that over-all efficiency is achieved by subjecting proteins to a time-sequence of multiple denaturation-renaturation cycles, resulting in gradual accumulation of the correctly folded protein. The method has proven efficient for a variety of recombinant proteins. Also provided are novel encrypted recognition sites for bovine coagulation factor X.sub.a. The encrypted recognition sites described may be activated in vitro by controlled oxidation or by reversible derivatization of cysteine residues and thereby generate new cleavage sites for factor X.sub.a. Two new recombinant serine protease exhibiting narrow substrate specificity for factor X.sub.a recognition sites are also provided. They may replace natural coagulation factor X.sub.a for cleavage of chimeric proteins.

Abstract: A DNA fragment distinct from the epidermal growth factor receptor (EGFR) and erbB-2 genes was detected by reduced stringency hybridization of v-erbB to normal genomic human DNA. cDNA cloning revealed a predicted 148 kd transmembrane polypeptide with structural features identifying it as a member of the erbB family, prompting designation of the new gene as erbB-3. It was shown to be expressed as a 6.2 kb transcript in a variety of normal tissues of epithelial origin. Markedly elevated erbB-3 mRNA levels were demonstrated in certain human mammary tumor cell lines. These findings indicate that increased erbB-3 expression, as in the case of EGFR and erbB-2, plays a role in some human malignancies. Using erbB-3 specific antibodies (polyclonal or monoclonal), the erbB-3 protein was identified as a 180 kDa glycoprotein, gp180.sup.erbB-3. The intrinsic catalytic function of gp180.sup.erbB-3 was uncovered by its ability to autophosphorylate in vitro.

Abstract: The present invention concerns the discovery of a new member of the TNF receptor superfamily, referred to herein as the candidate "tvb receptor". Experimental evidence suggests that the instant gene corresponds to the gene of the tvb.sup.s3 locus responsible for mediating certain viral infection. The tvb receptor plays a functional role as the receptor for certain of the avian leukosis/sarcoma viruses (ALSV) in avians, and a likely role as a receptor for tumor viruses in other animals, e.g., the feline leukemia virus and the like. Moreover, inspection of the tvb sequence, particularly in comparison with other TNF receptors, reveals the presence of a "death domain" in the cytoplasmic tail of the tvb receptor, suggesting a role for the tvb receptor in determining tissue fate and maintenance. For instance, the tvb genes and gene products may participate, under various circumstances, in the control of proliferation, differentiation and/or cell death.

Abstract: Quantitative reporter gene assays allowing for highly precise measurements of immunosuppressants in bodily fluids are provided, e.g., an IL-2 reporter gene assay for measuring blood levels of immunosuppressive cyclosporins and ascomycins (e.g., cyclosporin A and FK-506), and a c-jun reporter gene assay for measuring blood levels of immunosuppressive rapamycins.

Abstract: The invention provides methods and compositions relating to IKAP proteins which regulate cellular signal transduction and transcriptional activation, and related nucleic acids. The polypeptides may be produced recombinantly from transformed host cells from the disclosed IKAP encoding nucleic acids or purified from human cells. The invention provides isolated IKAP hybridization probes and primers capable of specifically hybridizing with the disclosed IKAP genes, IKAP-specific binding agents such as specific antibodies, and methods of making and using the subject compositions in diagnosis, therapy and in the biopharmaceutical industry.

Abstract: A novel human corticotropin releasing hormone (CRH) receptor which is a splice variant of the human CRH.sub.2 receptor subfamily and is designated human CRHR2.gamma.. Fragments of CRHR2.gamma.. Nucleic acid molecules which encode CRHR2.gamma. and fragments, expression vectors comprising the nucleic acid molecules, and host cells containing the expression vectors. Antibodies and antibody fragments capable of binding the novel receptor. Nucleic acid molecules capable of hybridizing with the above nucleic acid molecules. Use of the novel receptor and receptor fragments, antibodies and antibody fragments in testing compounds for CRH antagonist activity and in treating diseases.

Abstract: A synthetic human glucagon (hGlu) binding protein designated hGlu.DELTA.252-259 binding protein is cloned, expressed and used in an in vitro assay to screen for compounds that bind to the synthetic binding protein, including compounds that specifically stimulate or inhibit the binding of glucagon to the synthetic receptor. The invention includes the assay, the synthetic binding protein used in the assay, DNA encoding the synthetic binding protein, cells expressing the synthetic binding protein, and compounds identified through the use of the synthetic binding protein.