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 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: 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 method for treatment of a disease or condition in an organism characterized by an abnormal level of interaction between a BLM domain and its natural binding partner is described. The disease or condition may also be characterized by an abnormality in a signal transduction pathway, wherein the pathway contains a protein with a BLM domain. The method includes disrupting or promoting that interaction (or signal) in vivo. The method also involves inhibiting the activity of the complex formed between the BLM domain-containing protein and its natural binding partner. A method for diagnosis of such a disease or condition by detecting the level of such interaction as an indication of that disease or condition is also described. Also, a method for screening for an agent useful for treatment of such a disease or condition by assaying potential agents for the ability to disrupt or promote that interaction is described.

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: A novel receptor-type protein tyrosine phosphatase-.beta. (RPTP.beta.) protein or glycoprotein, and the DNA coding therefor is disclosed. This protein is naturally expressed in the brain and in neural cell lines. The RPTP.beta. 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 it phosphatase enzymatic activity, are provided.

Abstract: A novel receptor-type protein tyrosine phosphatase-.gamma. (RPTP.gamma.) protein or glycoprotein and the DNA coding therefor is expressed in a wide variety of mammalian tissues. The RPTP.gamma. 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.

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.alpha., human RPTP.beta. and human RPTP.gamma.. 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: 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 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).times.10.sup.-11 M. 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: A novel receptor-type protein tyrosine phosphatase-.kappa. (RPTP.kappa.) protein or glycoprotein and the DNA coding therefor is expressed in a wide variety of mammalian tissues. The RPTP.kappa. 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.kappa. molecules are provided.

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.alpha. or RPTP.epsilon. activity, elicit or modulate insulin receptor signal transduction are also described.

Abstract: A novel expression cloning method is provided for the detection, identification and purification of target proteins capable of binding at least to a tryosine-phosphorylated domain of a eukaryotic tyrosine kinase using novel peptide probes comprising an amino acid sequence substantially corresponding to a portion of a tyrosine-phosphorylated domain of a tyrosine kinase. The probe has at least one phosphorlated tyrosine residue and may be detectably labeled. Also disclosed is a method for preparing the probe, a method for mapping to a chormosome a gene encoding a protein capable of binding to tyrosine-phosphorylated domains of tyrosine kinases, and a method for purifiying such a protein with the probe. Non-limiting examples of novel proteins discovered using the above cloning method include GRB-1, GRB-2, GRB-3, GRB-4 and GRB-7, as well as nucleic acid encoding these proteins, and methods for detecting these proteins are also provided.

Abstract: A novel receptor-type protein tyrosine phosphatase-.kappa. (RPTP.kappa.) protein or glycoprotein and the DNA coding therefor is expressed in a wide variety of mammalian tissues. The RPTP.kappa. 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.kappa. molecules are provided.

Abstract: The present invention relates to a novel receptor-type protein tyrosine phosphatase protein or glycoprotein, termed RPTP.sigma. (also known as RPTPase-.sigma.), DNA coding therefor, antibodies specific for the protein or glycoprotein, methods for production and identification of the protein, methods for detection of nucleic acid encoding the protein, and methods for screening compounds capable of binding to and either inhibiting or stimulating RPTP.sigma. phosphatase activity.

Abstract: The present invention relates to a novel receptor-type protein tyrosine phosphatase protein or glycoprotein, termed RPTP.sigma. (also known as RPTPase-.sigma.), DNA coding therefor, antibodies specific for the protein or glycoprotein, methods for production and identification of the protein, methods for detection of nucleic acid encoding the protein, and methods for screening compounds capable of binding to and either inhibiting or stimulating RPTP.sigma. phosphatase activity.

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 feature 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 include 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 concerns methods for diagnosis and treatment of diseases or disorders characterized by abnormal cellular signal transduction involving a newly identified region, herein termed the "APB domain." APB domain binding between proteins is believed to play an important role in signal transduction pathways and, thereby, influence cellular events. Thus, APB mediated activity plays a role in signal transduction pathways and agents modulating APB mediated activity can be used to treat diseases or disorders involving proteins containing APB domains.

Abstract: The present invention relates to a method of treating in a mammal certain cancers, other cell proliferative diseases, and/or angiogenesis by using a salt or complex of a sulfated saccharide. The invention also relates to the use of mutant heparin binding growth factors that bind to the growth factor receptor, but not to heparin. The invention also provides pharmaceutical compositions for such methods.