src homology domains

Summary

Summary: Regions of sequence similarity in the src family of cytoplasmic tyrosine kinases. The SH1 domain is a catalytic domain. SH2 and SH3 domains are protein-binding domains. SH2 usually binds phosphotyrosine-containing proteins and SH3 interacts with cytoskeletal proteins.

Top Publications

  1. ncbi Coordinate activation of c-Src by SH3- and SH2-binding sites on a novel p130Cas-related protein, Sin
    K Alexandropoulos
    Massachusetts Institute of Technology, Cambridge, 02139, USA
    Genes Dev 10:1341-55. 1996
  2. ncbi A role for the podosome/invadopodia scaffold protein Tks5 in tumor growth in vivo
    Barbara Blouw
    Burnham Institute for Medical Research, Tumor Microenvironment Program, La Jolla, CA 92037, USA
    Eur J Cell Biol 87:555-67. 2008
  3. ncbi Systematic identification of SH3 domain-mediated human protein-protein interactions by peptide array target screening
    Chenggang Wu
    Department of Biochemistry and the Siebens Drake Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada
    Proteomics 7:1775-85. 2007
  4. ncbi The sulfogalactose moiety of sulfoglycosphingolipids serves as a mimic of tyrosine phosphate in many recognition processes. Prediction and demonstration of Src homology 2 domain/sulfogalactose binding
    Clifford Lingwood
    Research Institute, The Hospital for Sick Children, Toronto, Ontario M4G 1X8, Canada
    J Biol Chem 280:12542-7. 2005
  5. ncbi Adaptor FYB (Fyn-binding protein) regulates integrin-mediated adhesion and mediator release: differential involvement of the FYB SH3 domain
    L Geng
    Division of Tumor Immunology, Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston MA 02115-6084, USA
    Proc Natl Acad Sci U S A 98:11527-32. 2001
  6. ncbi p150Ship, a signal transduction molecule with inositol polyphosphate-5-phosphatase activity
    M N Lioubin
    Fred Hutchinson Cancer Research Center, Seattle, Washington 98104, USA
    Genes Dev 10:1084-95. 1996
  7. ncbi Organization of the SH3-SH2 unit in active and inactive forms of the c-Abl tyrosine kinase
    Bhushan Nagar
    Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley, 94720, USA
    Mol Cell 21:787-98. 2006
  8. ncbi Src-mediated tyrosine phosphorylation of dynamin is required for beta2-adrenergic receptor internalization and mitogen-activated protein kinase signaling
    S Ahn
    Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 274:1185-8. 1999
  9. ncbi Host response to EBV infection in X-linked lymphoproliferative disease results from mutations in an SH2-domain encoding gene
    A J Coffey
    The Sanger Centre, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, UK
    Nat Genet 20:129-35. 1998
  10. ncbi Targeted disruption of SHIP leads to hemopoietic perturbations, lung pathology, and a shortened life span
    C D Helgason
    Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada
    Genes Dev 12:1610-20. 1998

Research Grants

  1. INDUCTION OF MAMMARY CANCER BY SIGNALING MOLECULES
    Steven Anderson; Fiscal Year: 2003
  2. Protein Packing Defects as Functional Markers and Drug Targets
    Ariel Fernandez; Fiscal Year: 2007
  3. STRUCTURE BASED THERMODYNAMIC STUDIES OF HIV-1 PROTEASE
    Ernesto Freire; Fiscal Year: 2007
  4. The Promoter or A Prostate Specific Gene, Cten
    SU LO; Fiscal Year: 2004
  5. STRUCTURE BASED THERMODYNAMIC STUDIES OF HIV-1 PROTEASE
    Ernesto Freire; Fiscal Year: 2004
  6. Role of Cten in Prostate Cancer
    Su Hao Lo; Fiscal Year: 2007
  7. Mechanism of DLC1-mediated tumor suppression
    Su Hao Lo; Fiscal Year: 2010
  8. DNA-DIRECTED EFFECTS OF FdUMP(N)
    WILLIAM GMEINER; Fiscal Year: 2007
  9. STRUCTURE BASED THERMODYNAMIC STUDIES OF HIV1 PROTEASE
    Ernesto Freire; Fiscal Year: 2000
  10. Structure Based Themodynamic Studies of HIV-1 Protease
    Ernesto Freire; Fiscal Year: 2010

Detail Information

Publications193 found, 100 shown here

  1. ncbi Coordinate activation of c-Src by SH3- and SH2-binding sites on a novel p130Cas-related protein, Sin
    K Alexandropoulos
    Massachusetts Institute of Technology, Cambridge, 02139, USA
    Genes Dev 10:1341-55. 1996
    ....
  2. ncbi A role for the podosome/invadopodia scaffold protein Tks5 in tumor growth in vivo
    Barbara Blouw
    Burnham Institute for Medical Research, Tumor Microenvironment Program, La Jolla, CA 92037, USA
    Eur J Cell Biol 87:555-67. 2008
    ..Our data potentially implicate a novel role of podosomes as mediators of tumor angiogenesis and support further exploration of how podosome formation and Tks5 expression contribute to tumor progression...
  3. ncbi Systematic identification of SH3 domain-mediated human protein-protein interactions by peptide array target screening
    Chenggang Wu
    Department of Biochemistry and the Siebens Drake Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada
    Proteomics 7:1775-85. 2007
    ....
  4. ncbi The sulfogalactose moiety of sulfoglycosphingolipids serves as a mimic of tyrosine phosphate in many recognition processes. Prediction and demonstration of Src homology 2 domain/sulfogalactose binding
    Clifford Lingwood
    Research Institute, The Hospital for Sick Children, Toronto, Ontario M4G 1X8, Canada
    J Biol Chem 280:12542-7. 2005
    ..c-Src/Src homology domain 2:SGC/phosphogalactosylceramide binding confirms our hypothesis, heralding a carbohydrate-based approach to regulation of phosphotyrosine-mediated recognition...
  5. ncbi Adaptor FYB (Fyn-binding protein) regulates integrin-mediated adhesion and mediator release: differential involvement of the FYB SH3 domain
    L Geng
    Division of Tumor Immunology, Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston MA 02115-6084, USA
    Proc Natl Acad Sci U S A 98:11527-32. 2001
    ..Our findings identify FYB as a regulator of integrin-mediated adhesion and degranulation events, which, in the case of mast cells, has potential applications to inflammatory and allergic responses...
  6. ncbi p150Ship, a signal transduction molecule with inositol polyphosphate-5-phosphatase activity
    M N Lioubin
    Fred Hutchinson Cancer Research Center, Seattle, Washington 98104, USA
    Genes Dev 10:1084-95. 1996
    ..Ectopic expression of p150 in fibroblasts does not inhibit growth. This novel protein, p150(ship) (SH2-containing inositol phosphatase), identifies a component of a new growth factor-receptor signaling pathway in hematopoietic cells...
  7. ncbi Organization of the SH3-SH2 unit in active and inactive forms of the c-Abl tyrosine kinase
    Bhushan Nagar
    Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley, 94720, USA
    Mol Cell 21:787-98. 2006
    ..This alternative conformation of Abl is likely to prolong the active state of the kinase by preventing it from returning to the autoinhibited state...
  8. ncbi Src-mediated tyrosine phosphorylation of dynamin is required for beta2-adrenergic receptor internalization and mitogen-activated protein kinase signaling
    S Ahn
    Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 274:1185-8. 1999
    ..Thus, agonist-induced, c-Src-mediated tyrosine phosphorylation of dynamin is essential for its function in clathrin mediated G protein-coupled receptor endocytosis...
  9. ncbi Host response to EBV infection in X-linked lymphoproliferative disease results from mutations in an SH2-domain encoding gene
    A J Coffey
    The Sanger Centre, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, UK
    Nat Genet 20:129-35. 1998
    ..SH2D1A is expressed in many tissues involved in the immune system. The identification of SH2D1A will allow the determination of its mechanism of action as a possible regulator of the EBV-induced immune response...
  10. ncbi Targeted disruption of SHIP leads to hemopoietic perturbations, lung pathology, and a shortened life span
    C D Helgason
    Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada
    Genes Dev 12:1610-20. 1998
    ..Thus, homozygous disruption of SHIP establishes the crucial role of this molecule in modulating cytokine signaling within the hemopoietic system and provides a powerful model for further delineating its function...
  11. ncbi The Tensin-3 protein, including its SH2 domain, is phosphorylated by Src and contributes to tumorigenesis and metastasis
    Xiaolan Qian
    Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Cancer Cell 16:246-58. 2009
    ..Thus, tensin-3 is implicated as an oncoprotein regulated by Src and possessing an SH2 domain with a previously undescribed mechanism for the regulation of ligand binding...
  12. ncbi The X-linked lymphoproliferative-disease gene product SAP regulates signals induced through the co-receptor SLAM
    J Sayos
    Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    Nature 395:462-9. 1998
    ..Absence of the inhibitor SAP in XLP patients affects T/B-cell interactions induced by SLAM, leading to an inability to control B-cell proliferation caused by Epstein-Barr virus infections...
  13. ncbi The crystal structure of HIV-1 Nef protein bound to the Fyn kinase SH3 domain suggests a role for this complex in altered T cell receptor signaling
    S Arold
    Centre de Biochimie Structurale, UMR C9955 CNRS, U414 INSERM, Universite Montpellier I, Faculte de Pharmacie, France
    Structure 5:1361-72. 1997
    ....
  14. ncbi The SH3 domain--a family of versatile peptide- and protein-recognition module
    Tomonori Kaneko
    Department of Biochemistry and the Siebens Drake Medical Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario N6A 5C1, Canada
    Front Biosci 13:4938-52. 2008
    ....
  15. ncbi Targeting Stat3 in cancer therapy
    Naijie Jing
    Department of Medicine and Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA
    Anticancer Drugs 16:601-7. 2005
    ....
  16. ncbi Inactivating mutations in an SH2 domain-encoding gene in X-linked lymphoproliferative syndrome
    K E Nichols
    Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, MA 02129, USA
    Proc Natl Acad Sci U S A 95:13765-70. 1998
    ..Induction of DSHP may sustain the immune response by interfering with SHIP-mediated inhibition of lymphocyte activation, while its inactivation in XLP patients results in a selective immunodeficiency to EBV...
  17. ncbi Regulation of IRSp53-dependent filopodial dynamics by antagonism between 14-3-3 binding and SH3-mediated localization
    Jeffrey M Robens
    RGS Group, Institute of Medical Biology, Singapore 138673, Singapore
    Mol Cell Biol 30:829-44. 2010
    ....
  18. ncbi A potent and highly specific FN3 monobody inhibitor of the Abl SH2 domain
    John Wojcik
    Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois, USA
    Nat Struct Mol Biol 17:519-27. 2010
    ..This work provides a design guideline for highly specific and potent inhibitors of a protein interaction domain and shows their utility in mechanistic and cellular investigations...
  19. ncbi SH2 domains, interaction modules and cellular wiring
    T Pawson
    Programme in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, M5G 1X5, Toronto, Canada
    Trends Cell Biol 11:504-11. 2001
    ..We discuss the idea that rewiring of the cell's interaction network by pathogenic microorganisms and mutant cellular proteins contributes to dysregulation of cell signaling and thus to disease...
  20. ncbi SH2 domains: modulators of nonreceptor tyrosine kinase activity
    Panagis Filippakopoulos
    Structural Genomics Consortium, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Headington, Oxford OX3 7DQ, UK
    Curr Opin Struct Biol 19:643-9. 2009
    ..Here we summarize our understanding of mechanisms that lead to tyrosine kinase activation by direct interactions mediated by the SH2 domain and discuss how mutations in the SH2 domain trigger kinase inactivation...
  21. ncbi The pleckstrin homology domain: an intriguing multifunctional protein module
    G Shaw
    University of Florida College of Medicine, Department of Neuroscience, Gainesville 32610, USA
    Bioessays 18:35-46. 1996
    ..Numerous recent studies show that PH domains bind various proteins and inositolphosphates. Here I discuss PH domains in detail and conclude that they form a versatile family of membrane binding and protein localization modules...
  22. ncbi Two novel Src homology 2 domain proteins interact to regulate dictyostelium gene expression during growth and early development
    Christopher Sugden
    School of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, United Kingdom
    J Biol Chem 285:22927-35. 2010
    ..Thus, just as in metazoa, but on a vastly reduced numerical scale, an interacting network of SH2 domain proteins regulates specific Dictyostelium gene expression...
  23. ncbi Hydrophobic interaction between the SH2 domain and the kinase domain is required for the activation of Csk
    Esa T Mikkola
    Division of Biochemistry, Department of Biosciences, Faculty of Biological and Environmental Sciences, University of Helsinki, FIN 00014 Helsinki, Finland
    J Mol Biol 399:618-27. 2010
    ....
  24. ncbi The SH3 domain of amphiphysin binds the proline-rich domain of dynamin at a single site that defines a new SH3 binding consensus sequence
    D Grabs
    Department of Cell Biology and Howard Hughes Medical Institute, Yale University School of Medicine, Boyer Center for Molecular Medicine, New Haven, Connecticut 06510, USA
    J Biol Chem 272:13419-25. 1997
    ..Our data demonstrate that the long proline-rich stretch present in dynamin I contained multiple SH3 domain binding sites that recognize interacting proteins with high specificity...
  25. ncbi The propagation of binding interactions to remote sites in proteins: analysis of the binding of the monoclonal antibody D1.3 to lysozyme
    E Freire
    Department of Biology and Biocalorimetry Center, Johns Hopkins University, Baltimore, MD 21218, USA
    Proc Natl Acad Sci U S A 96:10118-22. 1999
    ..The low-stability regions might be involved in the transmission of binding information to other regions in the protein...
  26. ncbi Stattic: a small-molecule inhibitor of STAT3 activation and dimerization
    Jochen Schust
    Department of Molecular Biology, Independent Research Group, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany
    Chem Biol 13:1235-42. 2006
    ..We propose Stattic as a tool for the inhibition of STAT3 in cell lines or animal tumor models displaying constitutive STAT3 activation...
  27. ncbi Phosphorylation of SLP-76 by the ZAP-70 protein-tyrosine kinase is required for T-cell receptor function
    J Bubeck Wardenburg
    Center for Immunology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 271:19641-4. 1996
    ..As SLP-76 interacts with both Grb2 and phospholipase C-gamma1, these data indicate that phosphorylation of SLP-76 by ZAP-70 provides an important functional link between the T-cell receptor and activation of ras and calcium pathways...
  28. ncbi SHP-2 tyrosine phosphatase as an intracellular target of Helicobacter pylori CagA protein
    Hideaki Higashi
    Division of Molecular Oncology, Institute for Genetic Medicine and Graduate School of Science, Hokkaido University, Sapporo 060 0815, Japan
    Science 295:683-6. 2002
    ..Conversely, the CagA effect on cells was reproduced by constitutively active SHP-2. Thus, upon translocation, CagA perturbs cellular functions by deregulating SHP-2...
  29. ncbi Paxillin: a focal adhesion-associated adaptor protein
    M D Schaller
    Department of Cell and Developmental Biology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, NC 27599, USA
    Oncogene 20:6459-72. 2001
    ..The biological function of paxillin coordinated signaling is likely to regulate cell spreading and motility...
  30. ncbi Tyrosine 319 in the interdomain B of ZAP-70 is a binding site for the Src homology 2 domain of Lck
    M Pelosi
    Molecular Immunology Unit, Institut Pasteur, 25 28 Rue du Docteur Roux, 75724 Paris Cedex 15, France
    J Biol Chem 274:14229-37. 1999
    ..Collectively, our findings indicate that Tyr319-mediated binding of the SH2 domain of Lck is crucial for ZAP-70 activation and consequently for the propagation of the signaling cascade leading to T-cell activation...
  31. ncbi Linear motif atlas for phosphorylation-dependent signaling
    Martin Lee Miller
    Center for Biological Sequence Analysis, Technical University of Denmark, 2800 Lyngby, Denmark
    Sci Signal 1:ra2. 2008
    ..The atlas is available as a community resource (http://netphorest.info)...
  32. ncbi Characterization of domain-peptide interaction interface: a generic structure-based model to decipher the binding specificity of SH3 domains
    Tingjun Hou
    Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, California 92093, USA
    Mol Cell Proteomics 8:639-49. 2009
    ..The success of our framework on SH3 domains suggests that it is possible to establish a theoretical model to decipher the protein recognition code of any modular domain...
  33. ncbi Generating a panel of highly specific antibodies to 20 human SH2 domains by phage display
    K Pershad
    Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA
    Protein Eng Des Sel 23:279-88. 2010
    ....
  34. ncbi Structure-based prediction of the Saccharomyces cerevisiae SH3-ligand interactions
    Gregorio Fernandez-Ballester
    Instituto de Biologia Molecular y Celular, Universidad Miguel Hernandez, Edificio Torregaitan, Elche, Alicante, Spain
    J Mol Biol 388:902-16. 2009
    ..The success of this methodology opens the way for sequence-based, genome-wide prediction of protein-protein interactions given enough structural coverage...
  35. ncbi Nephrocystin-1 and nephrocystin-4 are required for epithelial morphogenesis and associate with PALS1/PATJ and Par6
    Marion Delous
    INSERM, U 574, Hopital Necker Enfants Malades, Paris, France
    Hum Mol Genet 18:4711-23. 2009
    ..Taken together, these results demonstrate that the nephrocystins play an essential role in epithelial cell organization, suggesting a plausible mechanism by which the in vivo histopathologic features of NPH might develop...
  36. ncbi The SRC homology 2 domain of Rin1 mediates its binding to the epidermal growth factor receptor and regulates receptor endocytosis
    M Alejandro Barbieri
    Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110-7463, USA
    J Biol Chem 278:32027-36. 2003
    ..These results indicate that Rin1 provides a link via its SH2 domain between activated tyrosine kinase receptors and the endocytic pathway through the recruitment and activation of Rab5a...
  37. ncbi Enhanced hematopoiesis by hematopoietic progenitor cells lacking intracellular adaptor protein, Lnk
    Satoshi Takaki
    Division of Immunology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108 8639, Japan
    J Exp Med 195:151-60. 2002
    ..These observations indicate that Lnk plays critical roles in the expansion and function of early hematopoietic progenitors, and provide useful clues for the amplification of hematopoietic progenitor cells...
  38. ncbi Interaction domains: from simple binding events to complex cellular behavior
    Tony Pawson
    Samuel Lumenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada M5G 1 X5
    FEBS Lett 513:2-10. 2002
    ..Here, we discuss the basic features of interaction domains, and suggest that rather simple binary interactions can be used in sophisticated ways to generate complex cellular responses...
  39. ncbi Jaks and cytokine receptors--an intimate relationship
    Claude Haan
    , University of Luxembourg, , L-1511 Luxembourg, Luxembourg
    Biochem Pharmacol 72:1538-46. 2006
    ..e. those with an associated Jak) would be enriched at the cell surface...
  40. ncbi Structural insights into phosphoinositide 3-kinase activation by the influenza A virus NS1 protein
    Benjamin G Hale
    Biomedical Science Research Complex, University of St Andrews, North Haugh, St Andrews, Fife, KY16 9ST, United Kingdom
    Proc Natl Acad Sci U S A 107:1954-9. 2010
    ..Overall, these data suggest that both direct binding of NS1 to p85beta (resulting in repositioning of the N-terminal SH2 domain) and possible NS1:p110 contacts contribute to PI3K activation...
  41. ncbi Nephrocystin interacts with Pyk2, p130(Cas), and tensin and triggers phosphorylation of Pyk2
    T Benzing
    Renal Division, University Hospital Freiburg, 79106 Freiburg, Germany and Children s Hospital, and Molecular Medicine, University of Freiburg, 79106 Freiburg, Germany
    Proc Natl Acad Sci U S A 98:9784-9. 2001
    ..A lack of functional nephrocystin may compromise Pyk2 signaling in a subset of renal epithelial cells...
  42. ncbi A mouse with a loss-of-function mutation in the c-Cbl TKB domain shows perturbed thymocyte signaling without enhancing the activity of the ZAP-70 tyrosine kinase
    Christine B F Thien
    Department of Pathology, University of Western Australia, Crawley, WA 6009, Australia
    J Exp Med 197:503-13. 2003
    ..Furthermore, the enhanced signaling in CD4(+)CD8(+) double positive thymocytes appears to be compensated by the selective down-regulation of CD3 on mature thymocytes and peripheral T cells from both strains of mutant c-Cbl mice...
  43. ncbi A remote substrate docking mechanism for the tec family tyrosine kinases
    Raji E Joseph
    Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, Iowa 50011, USA
    Biochemistry 46:5595-603. 2007
    ..This work is the first characterization of a substrate docking mechanism for the Tec kinases and provides evidence of a novel, phosphotyrosine-independent regulatory role for the ubiquitous SH2 domain...
  44. ncbi SH2 domains: role, structure and implications for molecular medicine
    Gabriel Waksman
    Washington University School of Medicine, Department of Biochemistry and Molecular Biophysics, Saint Louis, MO 63110, USA
    Expert Rev Mol Med 6:1-18. 2004
    ....
  45. ncbi RIN1 is an ABL tyrosine kinase activator and a regulator of epithelial-cell adhesion and migration
    Hailiang Hu
    David Geffen School of Medicine, Department of Biological Chemistry, Molecular Biology Institute, University of California, Los Angeles, Los Angeles, California 90095, USA
    Curr Biol 15:815-23. 2005
    ..These changes affect cell adhesion, cell migration, and cell-cell contact. Little is known, however, about upstream mechanisms regulating ABL protein activation...
  46. ncbi Mona, a novel hematopoietic-specific adaptor interacting with the macrophage colony-stimulating factor receptor, is implicated in monocyte/macrophage development
    R P Bourette
    Centre de Genetique Moleculaire et Cellulaire, UMR CNRS 5534, 43 Boulevard du 11 Novembre 1918, 69622 Villeurbanne Cedex, France
    EMBO J 17:7273-81. 1998
    ..Taken together, our results suggest an important role for Mona in the regulation of monocyte/macrophage development as controlled by M-CSF...
  47. ncbi Direct binding of the proline-rich region of protein tyrosine phosphatase 1B to the Src homology 3 domain of p130(Cas)
    F Liu
    Chemistry Department, Temple University, Philadelphia, Pennsylvania 19122, USA
    J Biol Chem 271:31290-5. 1996
    ..These results suggest that the proline-rich domain between amino acids 301 and 315 in PTP1B binds Src homology 3-containing proteins and that p130(Cas) may be a physiological target of this phosphatase in cells...
  48. ncbi Identification of Pex13p a peroxisomal membrane receptor for the PTS1 recognition factor
    R Erdmann
    Laboratory of Cell Biology, Howard Hughes Medical Institute, Rockefeller University, New York, New York 10021, USA
    J Cell Biol 135:111-21. 1996
    ....
  49. ncbi Pex13p is an SH3 protein of the peroxisome membrane and a docking factor for the predominantly cytoplasmic PTs1 receptor
    S J Gould
    Department of Biological Chemistry, Johns Hopkins University School of Medicine, Kennedy Krieger Institute, Baltimore, Maryland 21205, USA
    J Cell Biol 135:85-95. 1996
    ..We conclude that Pex13p functions as a docking factor for the predominantly cytoplasmic PTS1 receptor...
  50. ncbi Phospholipase C-gamma1 interacts with conserved phosphotyrosyl residues in the linker region of Syk and is a substrate for Syk
    C L Law
    Department of Microbiology, University of Washington, Seattle, USA
    Mol Cell Biol 16:1305-15. 1996
    ..Thus, an optimal kinase activity of Syk and an interaction between the linker region of Syk with PLC-gamma1 are required for the tyrosyl phosphorylation of PLC-gamma1...
  51. ncbi The human SHIP gene is differentially expressed in cell lineages of the bone marrow and blood
    S J Geier
    Fred Hutchinson Cancer Research Center, Seattle, WA 98104 2092, USA
    Blood 89:1876-85. 1997
    ..Furthermore, the expression of these protein species changes according to both the developmental stage and differentiated lineage of the mature blood cell...
  52. ncbi Interleukin-3 induces the association of the inositol 5-phosphatase SHIP with SHP2
    L Liu
    The Terry Fox Laboratory, British Columbia Cancer Agency, University of British Columbia, Vancouver, British Columbia V5Z 1L3, Canada
    J Biol Chem 272:10998-1001. 1997
    ..We further show that the association of SHIP with SHP2 occurs through the direct interaction of the SH2 domain of SHIP with a pYXN(I/V) sequence within SHP2...
  53. ncbi Regulation of the oncogenic activity of BCR-ABL by a tightly bound substrate protein RIN1
    D E Afar
    Department of Microbiology and Molecular Genetics, University of California, Los Angeles, 90095, USA
    Immunity 6:773-82. 1997
    ..RIN1 exemplifies a new class of effector molecules dependent on the concerted action of the SH3, SH2, and catalytic domains of a cytoplasmic tyrosine kinase...
  54. ncbi Mammalian SH2-containing protein tyrosine phosphatases
    M Adachi
    Cell 85:15. 1996
  55. ncbi The SH3 domain of the Saccharomyces cerevisiae peroxisomal membrane protein Pex13p functions as a docking site for Pex5p, a mobile receptor for the import PTS1-containing proteins
    Y Elgersma
    Department of Biochemistry, Academic Medical Centre, Amsterdam, The Netherlands
    J Cell Biol 135:97-109. 1996
    ..We therefore propose that Pex13p is a component of the peroxisomal protein import machinery onto which the mobile Pex5p receptor docks for the delivery of the selected PTS1 protein...
  56. ncbi A novel spliced form of SH2-containing inositol phosphatase is expressed during myeloid development
    D M Lucas
    Fred Hutchinson Cancer Research Center, Seattle, WA, USA
    Blood 93:1922-33. 1999
    ..However, experiments showed only a weak association of 135 kD SHIP with p85. A potentially analogous 135 kD SHIP species also appears in human differentiated leukocytes...
  57. ncbi Adaptor function for the Syk kinases-interacting protein 3BP2 in IL-2 gene activation
    M Deckert
    Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA
    Immunity 9:595-605. 1998
    ..Thus, 3BP2 is an important adaptor that may couple activated Zap-70/Syk to a LAT-containing signaling complex involved in TCR-mediated gene transcription...
  58. ncbi Interaction of the Grb7 adapter protein with Rnd1, a new member of the Rho family
    B Vayssiere
    Unité INSERM 248, Institut Curie, 26 Rue d Ulm, F 75248, Paris, France
    FEBS Lett 467:91-6. 2000
    ..The contribution of the interaction between Rnd1 and Grb7 to their respective functions and properties is discussed...
  59. ncbi Protein-tyrosine phosphatase alpha regulates Src family kinases and alters cell-substratum adhesion
    K W Harder
    Centre for Molecular Medicine and Therapeutics and the Department of Medicine, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada
    J Biol Chem 273:31890-900. 1998
    ....
  60. ncbi A single point mutation switches the specificity of group III Src homology (SH) 2 domains to that of group I SH2 domains
    Z Songyang
    Division of Signal Transduction, Beth Israel Hospital, Boston, Massachusetts, USA
    J Biol Chem 270:26029-32. 1995
    ..These results establish the importance of the beta D5 residue in determining specificities of SH2 domains...
  61. ncbi BCR-ABL SH3-SH2 domain mutations in chronic myeloid leukemia patients on imatinib
    Daniel W Sherbenou
    Cell and Developmental Biology, Oregon Health and Science University, Portland, OR, USA
    Blood 116:3278-85. 2010
    ..Regulatory domain mutations are uncommon but may explain resistance in some patients without mutations in the kinase domain...
  62. ncbi The adaptor protein Tks5/Fish is required for podosome formation and function, and for the protease-driven invasion of cancer cells
    Darren F Seals
    Van Andel Research Institute, Grand Rapids, Michigan 49503, USA
    Cancer Cell 7:155-65. 2005
    ..Thus, Tks5/Fish appears to be required for podosome formation, for degradation of the extracellular matrix, and for invasion of some cancer cells...
  63. ncbi A novel gene that encodes a protein with a putative src homology 3 domain is a candidate gene for familial juvenile nephronophthisis
    S Saunier
    INSERM U 423, Tour Lavoisier, 6 degrees étage, Hopital Necker Enfants Malades, 75743 Paris Cedex 15, France
    Hum Mol Genet 6:2317-23. 1997
    ..One of these mutations was found to segregate with the disease in the family, and the second appeared to be a de novo mutation. We therefore conclude that this novel gene is a strong candidate for NPH...
  64. ncbi MUC1 membrane trafficking is modulated by multiple interactions
    Carol L Kinlough
    Laboratory of Epithelial Cell Biology, Department of Medicine, Renal Electrolyte Division, University of Pittsburgh, Pittsburgh, PA 15261, USA
    J Biol Chem 279:53071-7. 2004
    ..This is the first indication that Grb2 plays a significant role in the endocytosis of MUC1...
  65. ncbi Structural basis for differential recognition of tyrosine-phosphorylated sites in the linker for activation of T cells (LAT) by the adaptor Gads
    Sangwoo Cho
    Center for Advanced Research in Biotechnology, WM Keck Laboratory for Structural Biology, University of Maryland Biotechnology Institute, Rockville, MD, USA
    EMBO J 23:1441-51. 2004
    ....
  66. ncbi Regulation of stem cell factor receptor signaling by Cbl family proteins (Cbl-b/c-Cbl)
    Shan Zeng
    Department of Dermatology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
    Blood 105:226-32. 2005
    ..The activated KIT in turn induces phosphorylation and activation of Cbl proteins. The Cbl proteins then bind and direct the degradation of activated KIT, leading to down-regulation of KIT signaling...
  67. ncbi Human homolog of disc-large is required for adherens junction assembly and differentiation of human intestinal epithelial cells
    Patrick Laprise
    Canadian Institutes of Health Research Group on Functional Development and Physiopathology of the Digestive Tract, Département d Anatomie et Biologie Cellulaire, Faculte de Medecine, Universite de Sherbrooke, Quebec J1H 5N4, Canada
    J Biol Chem 279:10157-66. 2004
    ..We conclude that hDlg may be a determinant in E-cadherin-mediated adhesion and signaling in mammalian epithelial cells...
  68. ncbi Subsets of the major tyrosine phosphorylation sites in Crk-associated substrate (CAS) are sufficient to promote cell migration
    Nah Young Shin
    Department of Cell and Developmental Biology, Vanderbilt Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    J Biol Chem 279:38331-7. 2004
    ..Effective wound healing was achieved by CAS variants containing as few as four of the major sites, indicating sufficiency of partial SD signaling function in this cell migration response...
  69. ncbi Molecular basis for a direct interaction between the Syk protein-tyrosine kinase and phosphoinositide 3-kinase
    Kyung D Moon
    Department of Medicinal Chemistry and Molecular Pharmacology and the Purdue Cancer Center, Purdue University, West Lafayette, Indiana 47907, USA
    J Biol Chem 280:1543-51. 2005
    ....
  70. ncbi Membrane localization and function of Vav3 in T cells depend on its association with the adapter SLP-76
    Celine Charvet
    Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA
    J Biol Chem 280:15289-99. 2005
    ..Altogether, our data show that TCR-induced association of Vav3 with SLP-76 is required for its membrane/IS localization and function...
  71. ncbi Identification of a switch in neurotrophin signaling by selective tyrosine phosphorylation
    Juan Carlos Arevalo
    Molecular Neurobiology Program, Skirball Institute of Biomolecular Medicine, Department of Cell Biology, New York University School of Medicine, NY 10016, USA
    J Biol Chem 281:1001-7. 2006
    ..Therefore, Trk receptor signaling involves an inducible switch mechanism through an unconventional substrate that distinguishes neurotrophin action from other growth factor receptors...
  72. ncbi SLAM-associated protein as a potential negative regulator in Trk signaling
    Kin Yip Lo
    Department of Biochemistry, Biotechnology Research Institute and Molecular Neuroscience Center, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China
    J Biol Chem 280:41744-52. 2005
    ..In summary, our findings demonstrated that SAP may serve as a negative regulator of Trk receptor activation and downstream signaling...
  73. ncbi Binding of the intracellular Fas ligand (FasL) domain to the adaptor protein PSTPIP results in a cytoplasmic localization of FasL
    Wiebke Baum
    Georg Speyer Haus, Paul Ehrlich Strasse 42 44, Frankfurt D 60596, Germany
    J Biol Chem 280:40012-24. 2005
    ..In addition, we demonstrate recruitment of the tyrosine phosphatase PTP-PEST by PSTPIP into FasL.PSTPIP.PTP-PEST complexes which may contribute to FasL reverse signaling...
  74. ncbi Crystal structures of a high-affinity macrocyclic peptide mimetic in complex with the Grb2 SH2 domain
    Jason Phan
    Macromolecular Crystallography Laboratory Center for Cancer Research, National Cancer Institute at Frederick, P.O. Box B, Frederick, MD 21702-1201, USA
    J Mol Biol 353:104-15. 2005
    ....
  75. ncbi Tyrosine phosphorylation of the well packed ephrinB cytoplasmic beta-hairpin for reverse signaling. Structural consequences and binding properties
    Jianxing Song
    Departments of Biochemistry and Biological Sciences, National University of Singapore, 10 Kent Ridge Crescent, Singapore
    J Biol Chem 278:24714-20. 2003
    ....
  76. ncbi Identification of Grb2 as a novel binding partner of the signaling lymphocytic activation molecule-associated protein binding receptor CD229
    Margarita Martin
    Unitat d Immunologia, Institut d Investigacions Biomediques August Pi i Sunyer, Departament de Biologia Cellular i Anatomia Patologica, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain
    J Immunol 174:5977-86. 2005
    ..Altogether, the data suggest a model whereby CD229 ligation attenuates TCR signaling and Grb2 recruitment to CD229 controls its rate of internalization...
  77. ncbi Regulation of FynT function by dual domain docking on PAG/Cbp
    Silje Anette Solheim
    Biotechnology Centre of Oslo and Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo, Gaustadalleen 21, Blindern, Oslo, Norway
    J Biol Chem 283:2773-83. 2008
    ..Thus, in T-cells, PAG is involved in positive as well as negative regulation of FynT activity...
  78. ncbi Kinetics of Src homology 3 domain association with the proline-rich domain of dynamins: specificity, occlusion, and the effects of phosphorylation
    Elena Solomaha
    Department of Neurobiology, Pharamacology, and Physiology, University of Chicago, IL 60637, USA
    J Biol Chem 280:23147-56. 2005
    ..Thus, differential binding of SH3 domain-containing proteins to dynamin-1 and -2 may contribute to the distinct functions performed by these isoforms...
  79. ncbi Structural insight into the binding diversity between the Tyr-phosphorylated human ephrinBs and Nck2 SH2 domain
    Xiaoyuan Ran
    Department of Biochemistry, National University of Singapore, 10 Kent Ridge Crescent, Singapore 119260
    J Biol Chem 280:19205-12. 2005
    ..In contrast, binding with [Tyr(P)330]ephrinB2(324-333) might have most residues over both halves engaged but induced less profound conformational dynamics on the mus-ms time scale...
  80. ncbi A novel proteomic screen for peptide-protein interactions
    Waltraud X Schulze
    Center for Experimental Bioinformatics, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense
    J Biol Chem 279:10756-64. 2004
    ..Our data are consistent with a change in the role of Sos from Ras-dependent signaling to actin remodeling/endocytic signaling events by a proline-SH3 domain switch...
  81. ncbi Adaptor ShcA protein binds tyrosine kinase Tie2 receptor and regulates migration and sprouting but not survival of endothelial cells
    Enrica Audero
    Division of Molecular Angiogenesis, Institute for Cancer Research and Treatment IRCC, School of Medicine, University of Torino, 10060 Candiolo, Italy
    J Biol Chem 279:13224-33. 2004
    ....
  82. ncbi Threonine phosphorylation of the beta 3 integrin cytoplasmic tail, at a site recognized by PDK1 and Akt/PKB in vitro, regulates Shc binding
    R I Kirk
    Department of Cell Biology and Anatomy, New York Medical College, Valhalla, New York 10595, USA
    J Biol Chem 275:30901-6. 2000
    ..These observations suggest that activation of PDK1 and/or Akt/PKB in platelets may modulate the binding activity and/or specificity of beta(3) for signaling molecules...
  83. ncbi Implication of the GRB2-associated phosphoprotein SLP-76 in T cell receptor-mediated interleukin 2 production
    D G Motto
    Department of Physiology, University of Iowa College of Medicine, Iowa City 52242, USA
    J Exp Med 183:1937-43. 1996
    ..Our data document the in vivo associations of SLP-76 with several proteins that potentially participate in T cell activation and implicate SLP-76 itself as an important molecule in TCR-mediated IL-2 production...
  84. ncbi The SH2 inositol 5-phosphatase Ship1 is recruited in an SH2-dependent manner to the erythropoietin receptor
    J M Mason
    Division of Cellular and Molecular Biology, Ontario Cancer Institute, University of Toronto, Toronto, Ontario M5G 2G1
    J Biol Chem 275:4398-406. 2000
    ..In contrast, EPO-dependent PKB activation was observed in EPO-RDelta43, but not in EPO-RDelta99. It appears that EPO-dependent PKB activation is downstream of a region that indirectly couples to phosphatidylinositol 3-kinase...
  85. ncbi Cloning and characterization of Lnk, a signal transduction protein that links T-cell receptor activation signal to phospholipase C gamma 1, Grb2, and phosphatidylinositol 3-kinase
    X Huang
    W Alton Jones Cell Science Center, Inc, Lake Placid, NY 12946, USA
    Proc Natl Acad Sci U S A 92:11618-22. 1995
    ....
  86. ncbi Independent SH2-binding sites mediate interaction of Dok-related protein with RasGTPase-activating protein and Nck
    P Lock
    Ludwig Institute for Cancer Research and the Cooperative Research Center for Cellular Growth Factors, P O Box 2008, Royal Melbourne Hospital, Parkville 3050, Australia
    J Biol Chem 274:22775-84. 1999
    ..Tandem SH2-binding sites containing Tyr-276 and Tyr-304 were shown to mediate binding of DokR to GAP, whereas Tyr-351 mediated the binding of DokR to Nck. These results suggest that DokR participates in numerous signaling pathways...
  87. ncbi Interaction of the adaptor protein Shc and the adhesion molecule cadherin
    Y Xu
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    J Biol Chem 272:13463-6. 1997
    ..Shc may therefore participate in the control of cell-cell adhesion as well as mitogenic signaling through Ras...
  88. ncbi Yes-associated protein and p53-binding protein-2 interact through their WW and SH3 domains
    X Espanel
    Department of Biochemistry and Molecular Biology, Mount Sinai School of Medicine, New York, New York 10029 6574, USA
    J Biol Chem 276:14514-23. 2001
    ..Since overexpression of an activated form of c-Yes resulted in tyrosine phosphorylation of p53BP-2, we propose that the p53BP-2 phosphorylation, possibly in the WW1 domain-binding motif, might negatively regulate the YAP.p53BP-2 complex...
  89. ncbi A model of activation of the protein tyrosine phosphatase SHP-2 by the human leptin receptor
    A Löthgren
    Pharmacia and Upjohn AB, Stockholm, Sweden
    Biochim Biophys Acta 1545:20-9. 2001
    ....
  90. ncbi Characterization of SH2D1A missense mutations identified in X-linked lymphoproliferative disease patients
    M Morra
    Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Biol Chem 276:36809-16. 2001
    ..Because no correlation is present between identified types of mutations and XLP patient clinical presentation, additional unidentified genetic or environmental factors must play a strong role in XLP disease manifestations...
  91. ncbi Multiple in vivo phosphorylated tyrosine phosphatase SHP-2 engages binding to Grb2 via tyrosine 584
    W Vogel
    Department of Molecular Biology, Max Planck Institut für Blochemie, Martinsried, Germany
    Cell Growth Differ 7:1589-97. 1996
    ..Immunoprecipitation of SHP-2 from a panel of mammary carcinoma cell lines copurifies several tyrosine phosphorylated proteins; the most prominent band has an apparent molecular weight of M(r) 115,000...
  92. ncbi The adaptor protein Gads (Grb2-related adaptor downstream of Shc) is implicated in coupling hemopoietic progenitor kinase-1 to the activated TCR
    S K Liu
    Department of Medical Biophysics and The Arthur and Sonia Labatt Brain Tumor Research Center, Hospital for Sick Children Research Institute, University of Toronto, Toronto, Ontario, Canada
    J Immunol 165:1417-26. 2000
    ..Together, these data suggest that HPK1 is involved in signaling downstream from the TCR, and that SH2/SH3 domain-containing adaptor proteins, such as Gads, may function to recruit HPK1 to the activated TCR complex...
  93. ncbi Differential association of cytoplasmic signalling molecules SHP-1, SHP-2, SHIP and phospholipase C-gamma1 with PECAM-1/CD31
    N J Pumphrey
    Division of Immunity and Infection, University of Birmingham, UK
    FEBS Lett 450:77-83. 1999
    ....
  94. ncbi Cloning and characterization of human Lnk, an adaptor protein with pleckstrin homology and Src homology 2 domains that can inhibit T cell activation
    Y Li
    School of Pharmacy, University of Maryland, Baltimore, MD 21201, USA
    J Immunol 164:5199-206. 2000
    ..The overexpression of Lnk in Jurkat cells led to an inhibition of anti-CD3 mediated NF-AT-Luc activation. Our study reveals a potentially new mechanism of T cell-negative regulation...
  95. ncbi Specificity of the SH2 domains of SHP-1 in the interaction with the immunoreceptor tyrosine-based inhibitory motif-bearing receptor gp49B
    L L Wang
    Howard Hughes Medical Institute, Rheumatology Division, Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    J Immunol 162:1318-23. 1999
    ..Thus, gp49B signaling involves SHP-1, and this association is dependent on tyrosine phosphorylation of the gp49B ITIMs, and an intact SHP-1 carboxyl SH2 domain...
  96. ncbi STAM2, a new member of the STAM family, binding to the Janus kinases
    K Endo
    Department of Microbiology, Tohoku University School of Medicine, Seiryo machi 2 1, Aoba ku, Sendai 980 8575, Japan
    FEBS Lett 477:55-61. 2000
    ....
  97. ncbi The germinal center kinase (GCK)-related protein kinases HPK1 and KHS are candidates for highly selective signal transducers of Crk family adapter proteins
    W Oehrl
    Laboratory of Molecular Oncology, Institute for Medical Radiation and Cell Research MSZ, Bavarian Julius Maximilians University, Wurzburg, Germany
    Oncogene 17:1893-901. 1998
    ..Furthermore, c-Crk II and, to a lesser extent, CRKL were substrates for HPK1. These results make it likely that HPK1 and KHS participate in the signal transduction of Crk family adapter proteins in certain cell types...
  98. ncbi NS5A, a nonstructural protein of hepatitis C virus, binds growth factor receptor-bound protein 2 adaptor protein in a Src homology 3 domain/ligand-dependent manner and perturbs mitogenic signaling
    S L Tan
    Department of Microbiology, School of Medicine, University of Washington, Seattle, WA 98195, USA
    Proc Natl Acad Sci U S A 96:5533-8. 1999
    ..Therefore, NS5A may function to perturb Grb2-mediated signaling pathways by selectively targeting the adaptor. These findings highlight a viral interceptor of cellular signaling with potential implications for HCV pathogenesis...
  99. ncbi Identification of vascular endothelial growth factor receptor-1 tyrosine phosphorylation sites and binding of SH2 domain-containing molecules
    N Ito
    Department of Medical Biochemistry and Microbiology, Uppsala University, Biomedical Center, Box 575, S 751 23 Uppsala, Sweden
    J Biol Chem 273:23410-8. 1998
    ..These results indicate that a spectrum of already known as well as novel phosphotyrosine-binding molecules are involved in signal transduction by Flt-1...
  100. ncbi Evidence for a direct interaction between insulin receptor substrate-1 and Shc
    A Kasus-Jacobi
    Centre de Recherche sur l Endocrinologie Moléculaire et le Développement du CNRS, UPR 1511, 92190 Meudon, France
    J Biol Chem 272:17166-70. 1997
    ..This study, describing a phosphotyrosine-dependent interaction between IRS-1 and Shc, suggests that this association might be important in signal transduction...
  101. ncbi Hematopoietic progenitor kinase 1 associates physically and functionally with the adaptor proteins B cell linker protein and SLP-76 in lymphocytes
    K Sauer
    Department of Immunology and Rheumatology and Department of Molecular Systems, Merck Research Laboratories, Rahway, New Jersey 07065, USA
    J Biol Chem 276:45207-16. 2001
    ....

Research Grants98

  1. INDUCTION OF MAMMARY CANCER BY SIGNALING MOLECULES
    Steven Anderson; Fiscal Year: 2003
    ..These studies will provide new information about the effect of the prolactin receptor upon mammary epithelial cells, and whether suppression of apoptosis in Important in mammary carcinogenesis. ..
  2. Protein Packing Defects as Functional Markers and Drug Targets
    Ariel Fernandez; Fiscal Year: 2007
    ..Thus, the novel design concept of "drug inhibitor as a wrapper of functional packing defects" will be explored and validated. ..
  3. STRUCTURE BASED THERMODYNAMIC STUDIES OF HIV-1 PROTEASE
    Ernesto Freire; Fiscal Year: 2007
    ..abstract_text> ..
  4. The Promoter or A Prostate Specific Gene, Cten
    SU LO; Fiscal Year: 2004
    ....
  5. STRUCTURE BASED THERMODYNAMIC STUDIES OF HIV-1 PROTEASE
    Ernesto Freire; Fiscal Year: 2004
    ....
  6. Role of Cten in Prostate Cancer
    Su Hao Lo; Fiscal Year: 2007
    ..Aim 3. To determine the function of cten in prostate physiology and carcinogenesis, using in vivo models of transgenic mice expressing wild-type or mutated human cten. ..
  7. Mechanism of DLC1-mediated tumor suppression
    Su Hao Lo; Fiscal Year: 2010
    ..The knowledge may apply to other cancers, since loss of DLC1 is associated with a variety of cancer types. ..
  8. DNA-DIRECTED EFFECTS OF FdUMP(N)
    WILLIAM GMEINER; Fiscal Year: 2007
    ..These studies greatly enrich our understanding of the unique cytotoxic mechanism for FdUMP[N] compounds towards PC cells. ..
  9. STRUCTURE BASED THERMODYNAMIC STUDIES OF HIV1 PROTEASE
    Ernesto Freire; Fiscal Year: 2000
    ..Differences in the type and strength of interactions will be evaluated and used to identify why some specific mutations affect the binding affinity of the substrate and inhibitor in different ways. ..
  10. Structure Based Themodynamic Studies of HIV-1 Protease
    Ernesto Freire; Fiscal Year: 2010
    ....
  11. STRUCTURE BASED THERMODYNAMIC STUDIES OF HIV-1 PROTEASE
    Ernesto Freire; Fiscal Year: 2005
    ....
  12. RABPHILIN3A AND EXOCYTOSIS AND CHROMAFFIN CELLS
    RONALD HOLZ; Fiscal Year: 2002
    ....
  13. REGULATION OF SUPEROXIDE PRODUCTION BY HUMAN NEUTROPHILS
    BERNARD BABIOR; Fiscal Year: 2003
    ..These studies may ultimately lead to new pharmacological methods for controlling oxygen radical-mediated tissue damage as well as an improved understanding of the pathophysiology of CGD. ..
  14. NEUTROPHIL PRIMING IN TRAUMA AND SEPSIS
    Michael Yaffe; Fiscal Year: 2009
    ....
  15. Signaling mechanisms that regulate meiosis in mammalian oocytes
    Lisa M Mehlmann; Fiscal Year: 2010
    ..The proposed studies will contribute to the basic science background that underlies such clinical advances. ..
  16. THROMBIN, SEPSIS AND MECHANISMS OF INFLAMMATION
    Chinnaswamy Tiruppathi; Fiscal Year: 2006
    ..abstract_text> ..
  17. Thrombin,Sepsis and Mechanisms of Inflammation
    Chinnaswamy Tiruppathi; Fiscal Year: 2007
    ..It is hoped that this work will lead to the development of new drug targeting acute lung injury associated with leaky lung microvessel and tissue edema formation. ..
  18. IDENTIFICATION OF TARGETS OF BCR ABL IN THE LEUKEMOGENIC
    Ruibao Ren; Fiscal Year: 2005
    ..These studies will help to further design rational therapeutic interventions for CML and to understand the mechanisms involved in leukemogenesis in general. ..
  19. A high- multiplexed phosphotyrosine profiling assay
    BRUCE MAYER; Fiscal Year: 2007
    ..They will also establish the feasibility of the OTM approach as a more general proteomic tool for the rapid and sensitive profiling of clinical samples. ..
  20. TUMOR CELL BIOLOGY OF THE FMS ONCOGENE PROTEINS
    LARRY ROHRSCHNEIDER; Fiscal Year: 1993
    ..These results will help to understand normal hematopoiesis and mechanisms that lead to the development of hematopoietic malignancies...
  21. TUMOR CELL BIOLOGY OF THE FMS ONCOGENE PROTEINS
    LARRY ROHRSCHNEIDER; Fiscal Year: 2000
    ..These studies will facilitate our understanding of why leukemias grow but fail at differentiation, and perhaps provide targets for rational intervention of growth or stimulation of differentiation. ..
  22. GENETICS OF RNA TUMOR VIRUSES
    G Martin; Fiscal Year: 2007
    ..The expression of certain Myc targets is rendered Myc- independent in v-Src-transformed cells, and the mechanism by which this occurs will be determined. ..
  23. GENETICS OF RNA TUMOR VIRUSES
    G Martin; Fiscal Year: 2002
    ..A complementation screen will be carried out to detect genes that complement transformation-defective mutants of v-Src. ..
  24. INTERLEUKIN 6 AND HUMAN BILIARY EPITHELIAL PROLIFERATION
    Anthony Demetris; Fiscal Year: 2000
    ..B. Use IL-6 antagonists, such as anti-IL6 monoclonal antibodies, suramin or inhibitors of intracellular second signaling molecules to determine if such interventions could have therapeutic implications for patients. ..
  25. INTERLEUKIN 6 AND HUMAN BILIARY EPITHELIAL PROLIFERATION
    Anthony Demetris; Fiscal Year: 2006
    ..abstract_text> ..
  26. GENETICS OF RNA TUMOR VIRUSES
    G Martin; Fiscal Year: 1980
    ..These mutants will be characterized by a variety of genetic and biochemical tests. Another approach involves the translation of subgenomic viral messenger RNAs isolated from virions or infected cells...
  27. Regulation of betaPIX Scaffolding Complexes by Non-canonical G Protein Signaling
    JAY JANZ; Fiscal Year: 2007
    ..Understanding the molecular details controlling these interactions will be critical in devising clinical strategies to prevent tumor metastasis and better design of therapeutics to treat cancer. ..
  28. MYOSIN DOMAIN INTERACTIONS DURING THE CONTRACTILE CYCLE
    Susan Lowey; Fiscal Year: 2007
    ....