Abstract: Crystals of the tyrosine kinase domain of cytoplasmic tyrosine kinases and receptor tyrosine kinases that undergo ligand-mediated receptor dimerization are provided. In particular, crystals of a mutant of the tyrosine kinase domain of fibroblast growth factor receptor 1 (FLGK), alone and in complex with a non-hydrolyzable adenosine triphosphate analogue, are provided. Also provided are the high resolution three dimensional structures of crystalline FLGK, both alone and in co-complex with the adenosine triphosphate analogue, as determined by X-ray diffraction.

Abstract: Methods for treatment, diagnosis, and screening are provided for diseases or conditions characterized by an abnormality in a signal transduction disorder. The signal transduction pathway involves an interaction between a PH domain and a PH domain binding partner.

Abstract: A novel receptor-type protein tyrosine phosphatase (RPTP) protein or glycoprotein and the DNA coding therefor is expressed in a wide variety of mammalian tissues. Included in this family of proteins are human RPTP&agr;, human RPTP&bgr; and human RPTP&ggr;. The RPTP protein or glycoprotein may be produced by recombinant means. Antibodies to the proteins, methods for measuring the quantity of the proteins, methods for screening compounds, such as drugs, which can bind to the proteins and inhibit or stimulate their activity, are provided.

Abstract: Crystals of the tyrosine kinase domain of cytoplasmic tyrosine kinases and receptor tyrosine kinases that undergo ligand-mediated receptor dimerization are provided. In particular, crystals of a mutant of the tyrosine kinase domain of fibroblast growth factor receptor 1 (FLGK), alone and in complex with a non-hydrolyzable adenosine triphosphate analogue, are provided. Also provided are the high resolution three dimensional structures of crystalline FLGK, both alone and in co-complex with the adenosine triphosphate analogue, as determined by X-ray diffraction.

Abstract: The present invention features a method for treatment of an organism having a disease or condition characterized by an abnormality in a signal transduction pathway, wherein the signal transduction pathway includes a PYK2 protein. The invention also features methods for diagnosing such diseases and for screening for agents that will be useful in treating such diseases. The invention also features purified and/or isolated nucleic acid encoding a PYK2 protein.

Abstract: The present invention features a method for treatment of an organism having a disease or condition characterized by an abnormality in a signal transduction pathway, wherein the signal transduction pathway includes a PYK2 protein. The invention also features methods for diagnosing such diseases and for screening for agents that will be useful in treating such diseases. The invention also features purified and/or isolated nucleic acid encoding a PYK2 protein.

Abstract: The present invention features a method for treatment of an organism having a disease or condition characterized by an abnormality in a signal transduction pathway, wherein the signal transduction pathway includes a rdgB protein. The invention also features methods for diagnosing such diseases and for screening for agents that will be useful in treating such diseases. The invention also features purified and/or isolated nucleic acid encoding a rdgB protein.

Abstract: The present invention relates to novel modalities of treatment of diabetes, and other diseases caused by dysfunctional signal transduction by insulin receptor type tyrosine kinases (IR-PTK). Applicants discovered that IR-PTK activity may be modified by modulating the activity of a tyrosine phosphatase, and IR-PTK signal transduction may be triggered even in the absence of ligand. Methods for identifying compounds that, by modulating RPTP&agr; or RPTP&egr; activity, elicit or modulate insulin receptor signal transduction are also described.

Abstract: The present invention relates to compositions and methods for the prevention and treatment of cell proliferative disorders wherein a protein tyrosine kinase or protein tyrosine phosphatase capable of complexing with a member of the SH2- and/or SH3-containing family of adaptor proteins is involved. This invention is based, in part, on the surprising discovery that the adaptor protein, GRB-2, binds the intracellular BCR-ABL tyrosine kinase product in vivo and is necessary for the activation of the oncogenic potential of the BCR/ABL product. The present invention further relates to protein tyrosine kinase/adaptor protein complexes and the uses of these complexes for the identification of agents capable of decreasing or inhibiting the interaction between the members of such complexes.

Abstract: The present invention relates to compositions and methods for the prevention and treatment of cell proliferative disorders wherein a protein tyrosine kinase or protein tyrosine phosphatase capable of complexing with a member of the SH2- and/or SH3-containing family of adaptor proteins is involved. This invention is based, in part, on the surprising discovery that the adaptor protein, GRB-2, binds the intracellular BCR-ABL tyrosine kinase product in vivo and is necessary for the activation of the oncogenic potential of the BCR/ABL product. The present invention further relates to protein tyrosine kinase/adaptor protein complexes and the uses of these complexes for the identification of agents capable of decreasing or inhibiting the interaction between the members of such complexes.

Abstract: A new class of receptor protein tyrosine phosphatase molecule, the families of ligands that binds this new class of receptor, and uses of such receptors and ligands is described.

Abstract: The present invention relates generally to a newly identified adaptor protein FRS2 and related products and methods. FRS2 links protein kinases to activating partners in cells. The invention also relates to nucleic acid molecules encoding portions of FRS2, nucleic acid vectors containing FRS2 related nucleic acid molecules, recombinant cells containing such nucleic acid vectors, polypeptides purified from such recombinant cells, antibodies to such polypeptides, and methods of identifying compounds that enhance or block FRS2 interactions with natural binding partners. Also disclosed are methods for diagnosing abnormal conditions in an organism with FRS2 related molecules or compounds.

Abstract: A novel receptor-type protein tyrosine phosphatase-&kgr; (RPTP&kgr;) protein or glycoprotein and the DNA coding therefor is expressed in a wide variety of mammalian tissues. The RPTP&kgr; protein or glycoprotein may be produced by recombinant means. Antibodies to the protein, methods for measuring the quantity of the protein, methods for screening compounds, such as drugs, which can bind to the protein and inhibit or stimulate their enzymatic activity, are provided. Further, methods for inhibiting homophilic binding of Type II RPTP, especially RPTP&kgr; molecules are provided.

Abstract: The present invention relates to a novel method, based on direct expression cloning, for identifying target proteins capable of binding to and/or serving as substrates for receptor or cytoplasmic tyrosine kinases. The present invention also relates to novel proteins identified using this method, and to methods for identifying compounds that disrupt the interaction of such novel proteins with the receptor or cytoplasmic tyrosine kinases.

Abstract: The present invention features a method for treatment of an organism having a disease or condition characterized by an abnormality in a signal transduction pathway, wherein the signal transduction pathway includes a PYK2 protein. The invention also features methods for diagnosing such diseases and for screening for agents that will be useful in treating such diseases. The invention also features purified and/or isolated nucleic acid encoding a PYK2 protein.

Abstract: The present invention relates to novel modalities of treatment of diabetes, and other diseases caused by dysfunctional signal transduction by insulin receptor type tyrosine kinases (IR-PTK). Applicants discovered that IR-PTK activity may be modified by modulating the activity of a tyrosine phosphatase, and IR-PTK signal transduction may be triggered even in the absence of ligand. Methods for identifying compounds that, by modulating RPTP&agr; or RPTP&egr; activity, elicit or modulate insulin receptor signal transduction are also described.

Abstract: The complete cDNA cloning of two human genes previously designated flg and bek is disclosed. These genes encode for two similar but distinct surface receptors comprised of an extracellular domain with three immunoglobulin-like regions, a single transmembrane domain, and a cytoplasmic portion containing a tyrosine kinase domain with a typical kinase insert. The expression of these two cDNAs in transfected NIH-3T3 cells led to the biosynthesis of proteins of 150 kDa and 135 kDa for flg and bek respectively. Direct binding experiments with radiolabeled acidic FGF (aFGF), basic FGF (bFGF), or kFGF inhibition of binding with native growth factors, and Scatchard analysis of the binding data indicated that bek and flg bind aFGF, bFGF, or kFGF with dissociation constants of (2-15)×10−11M. The high affinity binding of three distinct growth factors to each of two different receptors represents a unique double redundancy without precedence among polypeptide growth factor/receptor interactions.

Abstract: The present invention relates generally to a newly identified adaptor protein FRS2 and related products and methods. FRS2 links protein kinases to activating partners in cells. The invention also relates to nucleic acid molecules encoding portions of FRS2, nucleic acid vectors containing FRS2 related nucleic acid molecules, recombinant cells containing such nucleic acid vectors, polypeptides purified from such recombinant cells, antibodies to such polypeptides, and methods of identifying compounds that enhance or block FRS2 interactions with natural binding partners. Also disclosed are methods for diagnosing abnormal conditions in an organism with FRS2 related molecules or compounds.

Abstract: Hybridoma cell lines producing monoclonal antibodies specific to the human epidermal growth factor receptor are disclosed. The antibodies are capable of inhibiting the growth of human tumor cells expressing human epidermal growth factor receptors. Therapeutic uses of these monoclonal antibodies by themselves and in combination with anti-neoplastic agents are also disclosed.

Abstract: A novel receptor-type protein tyrosine phosphatase-.beta. (RPTP.beta.) protein or glycoprotein is disclosed. This protein is naturally expressed in the brain and in neural cell lines.