Abstract: The present invention provides transgenic non-human mammals and cells having one or more structurally and functionally disrupted NIK alleles. In addition, the present invention provides methods for making such transgenic mammals and cells, and methods for determining the effect of a compound on an animal or cell that lacks NIK function. The present invention also provides methods for identifying compounds useful in the inhibition of osteoclastogenesis in a mammal, for example to treat osteoporosis or other conditions. Also provided are methods of modulating the extent of osteoclastogenesis in a cell or a mammal using NIK modulators.

Abstract: Novel compositions and methods for inhibiting cytokine-induced intracellular activation of STAT family transcription factors by binding to the transcription factors and inhibiting the transcriptional activity of the factors are disclosed. The method comprises introducing into a cell an effective amount of a peptide or derivative thereof, in which the peptide contains a sequence that is derived from a receptor for the cytokine, but with a tyrosine residue being phosphorylated. The compositions comprise isolated peptides or derivatives thereof in which the peptide contains an amino acid sequence derived from a receptor for a cytokine but with a tyrosine residue phosphorylated. A method for identifying derivatives of the isolated peptides comprising detecting the inhibition of the binding of said peptide to a STAT family transcription factor by said derivative is also provided.

Abstract: Novel compositions and methods that result in the inactivation of IFN.gamma. inducible transcription factors by binding to the transcription factor in the cell and inhibiting the transcriptional activity of the factors are disclosed. The composition comprises an isolated peptide that contains the amino acid sequence Xaa.sub.1 -Asp-Xaa.sub.2 -Xaa.sub.3 -His SEQ ID No. 1 where Xaa.sub.1 is phosphorylated tyrosine and Xaa.sub.2 and Xaa.sub.3 are any amino acid, or derivatives and functional equivalents thereof, that is capable of specifically binding to the p91 family of IFN.gamma. inducible transcription factors in a cell. A method for inhibiting the intracellular activation of a transcription factor by introducing into a cell an effective amount of a peptide that contains the 5 amino acid sequence described or a derivative thereof, which specifically binds to a transcription factor in the cell is also provided.

Abstract: Novel compositions and methods that result in the inactivation of IFN.gamma. inducible transcription factors by binding to the transcription factor in the cell and inhibiting the transcriptional activity of the factors are disclosed. The composition comprises an isolated peptide that contains the amino acid sequence Xaa.sub.1 -Asp-Xaa.sub.2 -Xaa.sub.3 -His where Xaa.sub.1 is phosphorylated tyrosine and Xaa.sub.2 and Xaa.sub.3 are any amino acid, or derivatives and functional equivalents thereof, that is capable of specifically binding to the p91 family of IFN.gamma. inducible transcription factors in a cell. A method for inhibiting the intracellular activation of a transcription factor by introducing into a cell an effective amount of a peptide that contains the 5 amino acid sequence described or a derivative thereof, which specifically binds to a transcription factor in the cell is also provided.

Abstract: A murine monoclonal antibody combining site produced by a hybridoma formed by fusion of cells from a myeloma cell line and lymphocytes that produce antibodies that react (1) with isolated human C3b receptor and (2) with C3b receptor-bearing cells from a mammal immunized with human C3b receptor is disclosed.