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. pmc 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 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
  5. 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
  6. ncbi The importance of being proline: the interaction of proline-rich motifs in signaling proteins with their cognate domains
    B K Kay
    Department of Pharmacology, University of Wisconsin Madison, Madison, Wisconsin 53706 1532, USA
    FASEB J 14:231-41. 2000
  7. ncbi Mechanism of two classes of cancer mutations in the phosphoinositide 3-kinase catalytic subunit
    Nabil Miled
    Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK
    Science 317:239-42. 2007
  8. ncbi Defining the specificity space of the human SRC homology 2 domain
    Haiming Huang
    Department of Biochemistry, Siebens Drake Medical Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario N6A 5C1, Canada
    Mol Cell Proteomics 7:768-84. 2008
  9. pmc ABL tyrosine kinases: evolution of function, regulation, and specificity
    John Colicelli
    Department of Biological Chemistry, Molecular Biology Institute and Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
    Sci Signal 3:re6. 2010
  10. pmc Bayesian modeling of the yeast SH3 domain interactome predicts spatiotemporal dynamics of endocytosis proteins
    Raffi Tonikian
    Terrence Donnelly Center for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario, Canada
    PLoS Biol 7:e1000218. 2009

Detail Information

Publications246 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. pmc 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 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
    ....
  5. 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
    ....
  6. ncbi The importance of being proline: the interaction of proline-rich motifs in signaling proteins with their cognate domains
    B K Kay
    Department of Pharmacology, University of Wisconsin Madison, Madison, Wisconsin 53706 1532, USA
    FASEB J 14:231-41. 2000
    ..Kay, B. K., Williamson, M. P., Sudol, M. The importance of being proline: the interaction of proline-rich motifs in signaling proteins with their cognate domains...
  7. ncbi Mechanism of two classes of cancer mutations in the phosphoinositide 3-kinase catalytic subunit
    Nabil Miled
    Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK
    Science 317:239-42. 2007
    ..These studies extend our understanding of the architecture of PI3Ks and provide insight into how two classes of mutations that cause a gain in function can lead to cancer...
  8. ncbi Defining the specificity space of the human SRC homology 2 domain
    Haiming Huang
    Department of Biochemistry, Siebens Drake Medical Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario N6A 5C1, Canada
    Mol Cell Proteomics 7:768-84. 2008
    ..The definition of the specificity space of the human SH2 domain provides both the necessary molecular basis and a platform for future exploration of the functions for SH2-containing proteins in cells...
  9. pmc ABL tyrosine kinases: evolution of function, regulation, and specificity
    John Colicelli
    Department of Biological Chemistry, Molecular Biology Institute and Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
    Sci Signal 3:re6. 2010
    ..Information on ABL regulatory mechanisms is being mined to provide new therapeutic strategies against hematopoietic malignancies caused by BCR-ABL1 and related leukemogenic proteins...
  10. pmc Bayesian modeling of the yeast SH3 domain interactome predicts spatiotemporal dynamics of endocytosis proteins
    Raffi Tonikian
    Terrence Donnelly Center for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario, Canada
    PLoS Biol 7:e1000218. 2009
    ....
  11. ncbi Regulation of the c-Abl and Bcr-Abl tyrosine kinases
    Oliver Hantschel
    Developmental Biology Programme, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
    Nat Rev Mol Cell Biol 5:33-44. 2004
    ..Its oncogenic counterpart, the Bcr-Abl fusion protein, causes certain human leukaemias. Recent insights into the structure and regulation of the c-Abl and Bcr-Abl tyrosine kinases have changed the way we look at these enzymes...
  12. ncbi SNX9 couples actin assembly to phosphoinositide signals and is required for membrane remodeling during endocytosis
    Defne Yarar
    Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Dev Cell 13:43-56. 2007
    ..These results suggest a mechanism for the spatial and temporal regulation of N-WASP-dependent actin assembly and implicate SNX9 in directly coupling actin dynamics to membrane remodeling during multiple modes of endocytosis...
  13. ncbi Nck adaptor proteins link nephrin to the actin cytoskeleton of kidney podocytes
    Nina Jones
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada
    Nature 440:818-23. 2006
    ..Simple and widely expressed SH2/SH3 adaptor proteins can therefore direct the formation of a specialized cellular morphology in vivo...
  14. ncbi p130Cas, a substrate associated with v-Src and v-Crk, localizes to focal adhesions and binds to focal adhesion kinase
    M T Harte
    Department of Microbiology and Cancer Center, University of Virginia, Health Sciences Center, Charlottesville, Virginia 22908, USA
    J Biol Chem 271:13649-55. 1996
    ..The association of p130(Cas) with pp125(FAK), a kinase which is activated upon cell adhesion, is likely to be functionally important in integrin mediated signal transduction...
  15. pmc The multiple-specificity landscape of modular peptide recognition domains
    David Gfeller
    Banting and Best Department of Medical Research, The Donnelly Centre, University of Toronto, Toronto, Ontario, Canada
    Mol Syst Biol 7:484. 2011
    ..Overall, our results reveal a rich specificity landscape in peptide recognition domains, suggesting new ways of encoding specificity in protein interaction networks...
  16. ncbi Phosphatidylinositol 4,5-biphosphate (PIP2)-induced vesicle movement depends on N-WASP and involves Nck, WIP, and Grb2
    Stefanie Benesch
    Department of Cell Biology, Gesellschaft fur Biotechnologische Forschung GBF, Mascheroder Weg 1, D 38124 Braunschweig, Germany
    J Biol Chem 277:37771-6. 2002
    ....
  17. 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...
  18. ncbi Signaling pathways and structural domains required for phosphorylation of EMS1/cortactin
    D H Campbell
    Cancer Research Program, Garvan Institute of Medical Research, St Vincent s Hospital, Sydney, New South Wales, Australia
    Cancer Res 59:5376-85. 1999
    ..These data identify MEK as an important intermediate involved in EMS1 phosphorylation and highlight the helical-proline-rich region as a key regulatory domain...
  19. pmc The 145-kDa protein induced to associate with Shc by multiple cytokines is an inositol tetraphosphate and phosphatidylinositol 3,4,5-triphosphate 5-phosphatase
    J E Damen
    The Terry Fox Laboratory, British Columbia Cancer Agency, University of British Columbia, Vancouver, Canada
    Proc Natl Acad Sci U S A 93:1689-93. 1996
    ..This novel signal transduction intermediate may serve to modulate both Ras and inositol signaling pathways. Based on its properties, we suggest the 145-kDa protein be called SHIP for SH2-containing inositol phosphatase...
  20. doi Avian and 1918 Spanish influenza a virus NS1 proteins bind to Crk/CrkL Src homology 3 domains to activate host cell signaling
    Leena S Heikkinen
    Department of Virology, Haartman Institute, University of Helsinki and Helsinki University Central Hospital, Haartmaninkatu 3 POB 21, FIN 00014, Helsinki, Finland
    J Biol Chem 283:5719-27. 2008
    ..Thus, the Spanish Flu virus resembles avian influenza A viruses in its ability to recruit Crk/CrkL to modulate host cell signaling...
  21. pmc The src homology 2-containing inositol phosphatase (SHIP) is the gatekeeper of mast cell degranulation
    M Huber
    Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada V5Z 1L3
    Proc Natl Acad Sci U S A 95:11330-5. 1998
    ..These results show the critical role that SHIP plays in setting the threshold for degranulation and that SHIP directly modulates a "positive-acting" receptor...
  22. ncbi Crystal structure of the tyrosine phosphatase SHP-2
    P Hof
    Joslin Diabetes Center and the Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    Cell 92:441-50. 1998
    ..Recognition of bisphosphorylated ligands by the tandem SH2 domains is an integral element of this switch; the C-terminal SH2 domain contributes binding energy and specificity, but it does not have a direct role in activation...
  23. ncbi SH3-Domain binding function of HIV-1 Nef is required for association with a PAK-related kinase
    A Manninen
    Institute of Medical Technology, University of Tampere, Tampere, FIN 33101, Finland
    Virology 250:273-82. 1998
    ..Molecular modeling suggests that these residues are involved in formation of an adjacent binding surface for NAK or another critical component of the NAK/Nef complex...
  24. pmc SH2 domains recognize contextual peptide sequence information to determine selectivity
    Bernard A Liu
    Ben May Department for Cancer Research and Committee on Cancer Biology, The University of Chicago, Chicago, Illinois 60637, USA
    Mol Cell Proteomics 9:2391-404. 2010
    ..This concept may serve more broadly as a paradigm for subtle recognition of physiological ligands by protein interaction domains...
  25. ncbi Three-dimensional structure of the tyrosine kinase c-Src
    W Xu
    Laboratory of Molecular Medicine, Children s Hospital, Boston, Massachusetts 02115, USA
    Nature 385:595-602. 1997
    ..The structure shows how appropriate cellular signals, or transforming mutations in v-Src, could break these interactions to produce an open, active kinase...
  26. ncbi Cytokine-inducible SH2 protein-3 (CIS3/SOCS3) inhibits Janus tyrosine kinase by binding through the N-terminal kinase inhibitory region as well as SH2 domain
    A Sasaki
    Institute of Life Science, Kurume University, Aikawa machi 2432 3 Kurume 839 0861, Japan
    Genes Cells 4:339-51. 1999
    ..We also identified another JAK-binding protein, CIS3 (cytokine-inducible SH2-protein 3, or SOCS3) that inhibits signalling of various cytokines. However, the mechanism of JAK signal inhibition by CIS3 has not been clarified...
  27. ncbi SHP2 and SOCS3 contribute to Tyr-759-dependent attenuation of interleukin-6 signaling through gp130
    Ute Lehmann
    Department of Biochemistry, Rheinisch Westfälische Technische Hochschule Aachen, Pauwelsstrasse 30, Aachen D 52074, Germany
    J Biol Chem 278:661-71. 2003
    ..These data suggest, that there are two, largely distinct modes of negative regulation of gp130 activity, despite the fact that both SOCS3 and SHP2 are recruited to the same site within gp130...
  28. ncbi Regulation of Btk function by a major autophosphorylation site within the SH3 domain
    H Park
    Department of Microbiology and Molecular Genetics, University of California, Los Angeles 90095 1662, USA
    Immunity 4:515-25. 1996
    ..The location of Y223 in a potential ligand-binding pocket suggests that autophosphorylation regulates SH3-mediated signaling by Btk...
  29. pmc Tyrosine phosphorylation within the SH3 domain regulates CAS subcellular localization, cell migration, and invasiveness
    Radoslav Janostiak
    Department of Cell Biology, Charles University, 12843 Prague, Czech Republic
    Mol Biol Cell 22:4256-67. 2011
    ..These findings reveal an important role of CAS Y12 phosphorylation in the regulation of focal adhesion assembly, cell migration, and invasiveness of Src-transformed cells...
  30. ncbi HIV-1 Nef downregulates MHC-I by a PACS-1- and PI3K-regulated ARF6 endocytic pathway
    Anastassia D Blagoveshchenskaya
    Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA
    Cell 111:853-66. 2002
    ..These data provide new insights into the cellular basis of HIV-1 immunoevasion...
  31. ncbi Adaptor protein 3BP2 is a potential ligand of Src homology 2 and 3 domains of Lyn protein-tyrosine kinase
    Koichiro Maeno
    Division of Proteomics, Department of Genome Sciences, Kobe University Graduate School of Medicine, 7 5 1 Kusunoki cho, Chuo Ku, Japan
    J Biol Chem 278:24912-20. 2003
    ..These results suggest that the adaptor protein 3BP2 is a potential regulator of Lyn protein-tyrosine kinase as a ligand of its SH3/SH2 domains in FcepsilonRI-mediated signaling in mast cells...
  32. doi Transient structure and SH3 interaction sites in an intrinsically disordered fragment of the hepatitis C virus protein NS5A
    Sophie Feuerstein
    Institut de Biologie Structurale, Université Grenoble 1, 41 rue Jules Horowitz, 38027 Grenoble Cedex 1, France
    J Mol Biol 420:310-23. 2012
    ..The present work also highlights the power of NMR spectroscopy to characterize multiple binding events including short-lived transient interactions between globular and highly disordered proteins...
  33. doi Phosphorylation regulates tau interactions with Src homology 3 domains of phosphatidylinositol 3-kinase, phospholipase Cgamma1, Grb2, and Src family kinases
    C Hugh Reynolds
    The MRC Centre for Neurodegeneration Research, King s College London, Institute of Psychiatry, London, UK
    J Biol Chem 283:18177-86. 2008
    ....
  34. doi 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)...
  35. pmc The SH3p4/Sh3p8/SH3p13 protein family: binding partners for synaptojanin and dynamin via a Grb2-like Src homology 3 domain
    N Ringstad
    Department of Cell Biology and Howard Hughes Medical Institute, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06510, USA
    Proc Natl Acad Sci U S A 94:8569-74. 1997
    ..These findings underscore the important role of SH3-mediated interactions in synaptic vesicle recycling...
  36. pmc Insulin receptor tyrosine kinase substrate links the E. coli O157:H7 actin assembly effectors Tir and EspF(U) during pedestal formation
    Didier Vingadassalom
    Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Proc Natl Acad Sci U S A 106:6754-9. 2009
    ..Thus, enterohemorrhagic E. coli translocates 2 effectors that bind to distinct domains of a common host factor to promote the formation of a complex that triggers robust actin assembly at the plasma membrane...
  37. ncbi Reciprocal regulation of SH3 and SH2 domain binding via tyrosine phosphorylation of a common site in CD3epsilon
    Tapio Kesti
    Department of Virology, Haartman Institute, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland
    J Immunol 179:878-85. 2007
    ..Thus, phosphorylation of Y166 serves as a molecular switch during T cell activation that determines the capacity of CD3epsilon to interact with either SH3 or SH2 domain-containing proteins...
  38. ncbi Novel mode of ligand binding by the SH2 domain of the human XLP disease gene product SAP/SH2D1A
    S C Li
    Program in Molecular Biology and Cancer, Department of Molecular and Medical Genetics, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Canada
    Curr Biol 9:1355-62. 1999
    ..The SAP-SLAM interaction can occur in a phosphorylation-independent manner...
  39. 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...
  40. pmc 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...
  41. pmc 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...
  42. 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...
  43. ncbi Structure, function, and biology of SHIP proteins
    L R Rohrschneider
    Fred Hutchinson Cancer Research Center, Division of Basic Sciences, Seattle, Washington 98109 1024, USA
    Genes Dev 14:505-20. 2000
  44. ncbi Biochemical properties of the Cdc42-associated tyrosine kinase ACK1. Substrate specificity, authphosphorylation, and interaction with Hck
    Noriko Yokoyama
    Department of Physiology and Biophysics, School of Medicine, State University of New York at Stony Brook, Stony Brook, New York 11794 8661, USA
    J Biol Chem 278:47713-23. 2003
    ..Our data suggest that Hck is a novel binding partner for ACK1 that can regulate ACK1 activity by phosphorylation...
  45. ncbi Activation of STAT3 by the Src family kinase Hck requires a functional SH3 domain
    Steven J Schreiner
    Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    J Biol Chem 277:45680-7. 2002
    ..These results support a model in which Src family kinases recruit STAT3 through an SH3-dependent mechanism, resulting in transient kinase activation and STAT3 phosphorylation...
  46. ncbi Can we infer peptide recognition specificity mediated by SH3 domains?
    Gianni Cesareni
    Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica, 00133 Rome, Italy
    FEBS Lett 513:38-44. 2002
    ..Finally, we will discuss whether the available information is sufficient to infer the recognition specificity of any uncharacterized SH3 domain...
  47. ncbi A novel, specific interaction involving the Csk SH3 domain and its natural ligand
    R Ghose
    The Rockefeller University, 1230 York Avenue, New York, New York 10021 6399, USA
    Nat Struct Biol 8:998-1004. 2001
    ..NMR relaxation analysis suggests that Csk-SH3 has different dynamic properties in the various subsites important for peptide recognition...
  48. 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...
  49. ncbi Regulation of p73 by c-Abl through the p38 MAP kinase pathway
    Ricardo Sanchez-Prieto
    Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892 4330, USA
    Oncogene 21:974-9. 2002
    ..These findings indicate that members of the MAP kinases superfamily of signaling molecules can regulate p73, and support a role for the p38 MAP kinase in a novel biochemical pathway by which c-Abl regulates this p53-related molecule...
  50. pmc Cooperative interactions at the SLP-76 complex are critical for actin polymerization
    Mira Barda-Saad
    Mina and Everard Goodman Faculty of Life Sciences, Bar Ilan University, Ramat Gan, Israel
    EMBO J 29:2315-28. 2010
    ..Disruption of the VAV1:Nck interaction deleteriously affected actin polymerization. These novel findings shed new light on the mechanism of actin polymerization after T-cell activation...
  51. pmc 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...
  52. doi Distinct binding modes of two epitopes in Gab2 that interact with the SH3C domain of Grb2
    Maria Harkiolaki
    Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX37BN, UK
    Structure 17:809-22. 2009
    ..In summary, our study reveals interaction types of SH3 domains, highlighting their great versatility...
  53. pmc Phosphorylated YDXV motifs and Nck SH2/SH3 adaptors act cooperatively to induce actin reorganization
    Ivan M Blasutig
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 1084 600 University Avenue, Toronto, Ontario M5G 1X5, Canada
    Mol Cell Biol 28:2035-46. 2008
    ..Together, these data identify pYDXV/Nck signaling as a potent and portable mechanism for physiological and pathological actin regulation...
  54. ncbi A new protein containing an SH2 domain that inhibits JAK kinases
    T A Endo
    Institute of Life Science, Kurume University, Aikawamachi, Japan
    Nature 387:921-4. 1997
    ..JAB and CIS appear to function as negative regulators in the JAK signalling pathway...
  55. ncbi Dynamin and the actin cytoskeleton cooperatively regulate plasma membrane invagination by BAR and F-BAR proteins
    Toshiki Itoh
    Department of Cell Biology and Howard Hughes Medical Institute, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    Dev Cell 9:791-804. 2005
    ..These results suggest a close interplay between the mechanisms that control actin dynamics and those that mediate plasma membrane invagination and fission...
  56. 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...
  57. ncbi Molecular basis of phosphorylation-induced activation of the NADPH oxidase
    Yvonne Groemping
    Division of Protein Structure, National Institute for Medical Research, Mill Hill, London NW7 1AA, UK
    Cell 113:343-55. 2003
    ..This permits p47(phox) to interact with the cytoplasmic tail of p22(phox) and initiate formation of the active, membrane bound enzyme complex...
  58. pmc A single amino acid in the SH3 domain of Hck determines its high affinity and specificity in binding to HIV-1 Nef protein
    C H Lee
    Laboratory of Molecular Biophysics, Rockefeller University, New York, NY 10021, USA
    EMBO J 14:5006-15. 1995
    ..The binding of a peptide containing the Nef PxxP motif showed > 300-fold weaker affinity for Hck SH3 than full-length Nef...
  59. ncbi SOCS3 exerts its inhibitory function on interleukin-6 signal transduction through the SHP2 recruitment site of gp130
    J Schmitz
    Institut fur Biochemie, Rheinisch Westfälische Technische Hochschule Aachen, Pauwelsstrabetae 30, D 52074 Aachen, Germany
    J Biol Chem 275:12848-56. 2000
    ..Besides SHP2, SOCS3 also interacts with the Tyr(P)-759 peptide of gp130. Taken together, our results suggest differences in the function of SOCS1 and SOCS3 and a link between SHP2 and SOCS3...
  60. 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...
  61. ncbi Analysis of Grb7 recruitment by heregulin-activated erbB receptors reveals a novel target selectivity for erbB3
    R J Fiddes
    Cancer Research Program, Garvan Institute of Medical Research, St Vincent s Hospital, Sydney, New South Wales 2010, Australia
    J Biol Chem 273:7717-24. 1998
    ..These studies therefore identify Grb7 as an in vivo target of erbB3 and erbB4 and provide an underlying mechanism for the ability of erbB3 to recruit Grb7 and not Grb2, a property unique among erbB receptors...
  62. ncbi Intersectin 2, a new multimodular protein involved in clathrin-mediated endocytosis
    C Pucharcos
    Down Syndrome Research Group, Medical and Molecular Genetics Center, IRO, Hospital Duran i Reynals, Avia de Castelldefels Km 2 7, L Hospitalet de Llobregat, 08907, Barcelona, Spain
    FEBS Lett 478:43-51. 2000
    ..Moreover, their overexpression, as well as the corresponding ITSN1 protein forms, inhibits transferrin internalization...
  63. ncbi Specificity in signal transduction: from phosphotyrosine-SH2 domain interactions to complex cellular systems
    Tony Pawson
    Samuel Lunenfeld Research Institute, Mt Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada
    Cell 116:191-203. 2004
    ..Here, I discuss experiments that have led to this view of dynamic cellular behavior and identify some current and future areas of interest in cell signaling...
  64. pmc Of bars and rings: Hof1-dependent cytokinesis in multiseptated hyphae of Ashbya gossypii
    Andreas Kaufmann
    Biozentrum, Basel, Switzerland
    Mol Cell Biol 29:771-83. 2009
    ..Simultaneously, a septum forms between the adjacent hyphal compartments, which do not separate. During evolution, A. gossypii lost the homologs of two enzymes essential for cell separation in Saccharomyces cerevisiae...
  65. doi Modulation of Lck function through multisite docking to T cell-specific adapter protein
    Stine Granum
    Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo, Box 1105, Blindern, N 0317 Oslo, Norway
    J Biol Chem 283:21909-19. 2008
    ..We propose that through multivalent interactions with Lck, TSAd diverts Lck from phosphorylating other substrates, thus modulating its functional activity through substrate competition...
  66. ncbi SAP couples Fyn to SLAM immune receptors
    Betty Chan
    Department of Cancer Biology, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
    Nat Cell Biol 5:155-60. 2003
    ..These findings broaden our understanding of the functional repertoire of SH3 and SH2 domains...
  67. ncbi The signaling adapter FRS-2 competes with Shc for binding to the nerve growth factor receptor TrkA. A model for discriminating proliferation and differentiation
    S O Meakin
    Neurodegeneration Research Group, The John P Robarts Research Institute, London, Ontario N6A 5K8, Canada
    J Biol Chem 274:9861-70. 1999
    ..Importantly, overexpression of FRS-2 in cells expressing an NGF nonresponsive TrkA receptor mutant reconstitutes the ability of NGF to stop cell cycle progression and to stimulate neuronal differentiation...
  68. ncbi Cloning of p97/Gab2, the major SHP2-binding protein in hematopoietic cells, reveals a novel pathway for cytokine-induced gene activation
    H Gu
    Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell 2:729-40. 1998
    ..Our results identify p97 as an important regulator of receptor signaling that controls a novel pathway to immediate-early gene activation and suggest multiple functions for SHP2 in cytokine receptor signaling...
  69. ncbi An activating immunoreceptor complex formed by NKG2D and DAP10
    J Wu
    DNAX Research Institute, 901 California Avenue, Palo Alto, CA 94304, USA
    Science 285:730-2. 1999
    ..Thus, NKG2D-DAP10 receptor complexes may activate NK and T cell responses against MICA-bearing tumors...
  70. pmc Crystal structure of the amphiphysin-2 SH3 domain and its role in the prevention of dynamin ring formation
    D J Owen
    MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK
    EMBO J 17:5273-85. 1998
    ..Our data suggest that amphiphysin SH3 domains are important regulators of the multimerization cycle of dynamin in endocytosis...
  71. ncbi The Wiskott-Aldrich syndrome protein-interacting protein (WIP) binds to the adaptor protein Nck
    I M Anton
    Division, Children s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 273:20992-5. 1998
    ..We demonstrate the presence of profilin in Nck precipitates suggesting that Nck may couple extracellular signals to the cytoskeleton via its interaction with WIP and profilin...
  72. 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
    ....
  73. 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
    ....
  74. 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...
  75. pmc 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...
  76. pmc 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...
  77. doi 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
    ....
  78. pmc 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...
  79. 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...
  80. pmc 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
    ....
  81. 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...
  82. 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...
  83. 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...
  84. 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...
  85. pmc 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...
  86. pmc 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
    ....
  87. doi 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...
  88. pmc 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...
  89. pmc 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...
  90. 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...
  91. ncbi Jaks and cytokine receptors--an intimate relationship
    Claude Haan
    Laboratoire de Biologie et Physiologie Intégrée LBPI, University of Luxembourg, 162A Avenue de la Faïencerie, L 1511 Luxembourg, Luxembourg
    Biochem Pharmacol 72:1538-46. 2006
    ..e. those with an associated Jak) would be enriched at the cell surface...
  92. pmc 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...
  93. 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...
  94. pmc 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...
  95. 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...
  96. 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...
  97. pmc 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...
  98. 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
    ....
  99. 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...
  100. 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...
  101. ncbi Mammalian SH2-containing protein tyrosine phosphatases
    M Adachi
    Cell 85:15. 1996

Research Grants110 found, 100 shown here

  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. Profiling Tumor Cells by SH2 Domain Binding Pattern
    BRUCE MAYER; Fiscal Year: 2002
    ..Variants of the existing profiling method will also be pursued, with the aim of developing a high-throughput method to quantitate binding sites for tens to hundreds of different SH2 domains in a single binding reaction. ..
  3. Functional Role of Nck and Crk Binding Interactions
    BRUCE MAYER; Fiscal Year: 2009
    ..The proposed studies will provide specific, mechanistic details about adaptor function that will provide insight into basic biological processes as well as how these processes can be subverted in disease. ..
  4. Functional Role of Nck and Crk Binding Interactions
    Bruce J Mayer; Fiscal Year: 2010
    ..The proposed studies will provide specific, mechanistic details about adaptor function that will provide insight into basic biological processes as well as how these processes can be subverted in disease. ..
  5. 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. ..
  6. Functional Role of Nck and Crk Binding Interactions
    BRUCE MAYER; Fiscal Year: 2007
    ..abstract_text> ..
  7. STRUCTURE BASED THERMODYNAMIC STUDIES OF HIV-1 PROTEASE
    Ernesto Freire; Fiscal Year: 2004
    ....
  8. STRUCTURE BASED THERMODYNAMIC STUDIES OF HIV-1 PROTEASE
    Ernesto Freire; Fiscal Year: 2007
    ..abstract_text> ..
  9. The Promoter or A Prostate Specific Gene, Cten
    SU LO; Fiscal Year: 2004
    ....
  10. 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. ..
  11. STRUCTURE BASED THERMODYNAMIC STUDIES OF HIV-1 PROTEASE
    Ernesto Freire; Fiscal Year: 2005
    ....
  12. 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. ..
  13. 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. ..
  14. 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. ..
  15. Structure Based Themodynamic Studies of HIV-1 Protease
    Ernesto Freire; Fiscal Year: 2010
    ....
  16. NEUTROPHIL PRIMING IN TRAUMA AND SEPSIS
    Michael Yaffe; Fiscal Year: 2009
    ....
  17. 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. ..
  18. 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. ..
  19. THROMBIN, SEPSIS AND MECHANISMS OF INFLAMMATION
    Chinnaswamy Tiruppathi; Fiscal Year: 2006
    ..abstract_text> ..
  20. 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. ..
  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. RABPHILIN3A AND EXOCYTOSIS AND CHROMAFFIN CELLS
    RONALD HOLZ; Fiscal Year: 2002
    ....
  23. 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. ..
  24. 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...
  25. 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...
  26. INTERLEUKIN 6 AND HUMAN BILIARY EPITHELIAL PROLIFERATION
    Anthony Demetris; Fiscal Year: 2006
    ..abstract_text> ..
  27. 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. ..
  28. 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. ..
  29. 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. ..