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 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
  2. ncbi A family of cytokine-inducible inhibitors of signalling
    R Starr
    The Walter and Eliza Hall Institute for Medical Research, Parkville, Victoria, Australia
    Nature 387:917-21. 1997
  3. 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
  4. ncbi Crystal structure of the Src family tyrosine kinase Hck
    F Sicheri
    Laboratories of Molecular Biophysics, The Rockefeller University, New York 10021, USA
    Nature 385:602-9. 1997
  5. 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
  6. 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
  7. 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
  8. 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
  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. ncbi Activation of Pak by membrane localization mediated by an SH3 domain from the adaptor protein Nck
    W Lu
    Howard Hughes Medical Institute, Children s Hospital, Boston, Massachusetts 02115, USA
    Curr Biol 7:85-94. 1997

Research Grants

Detail Information

Publications284 found, 100 shown here

  1. 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
    ....
  2. ncbi A family of cytokine-inducible inhibitors of signalling
    R Starr
    The Walter and Eliza Hall Institute for Medical Research, Parkville, Victoria, Australia
    Nature 387:917-21. 1997
    ..Transcription of all four SOCS genes is increased rapidly in response to interleukin-6, in vitro and in vivo, suggesting they may act in a classic negative feedback loop to regulate cytokine signal transduction...
  3. 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...
  4. ncbi Crystal structure of the Src family tyrosine kinase Hck
    F Sicheri
    Laboratories of Molecular Biophysics, The Rockefeller University, New York 10021, USA
    Nature 385:602-9. 1997
    ..The conformation of the active site has similarities with that of inactive cyclin-dependent protein kinases...
  5. 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)...
  6. 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
    ....
  7. 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...
  8. 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...
  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. ncbi Activation of Pak by membrane localization mediated by an SH3 domain from the adaptor protein Nck
    W Lu
    Howard Hughes Medical Institute, Children s Hospital, Boston, Massachusetts 02115, USA
    Curr Biol 7:85-94. 1997
    ..The Pak family of serine/threonine kinases are known to be activated by binding to the GTP-bound form of Cdc42 or Rac1, which are small GTPases of the Rho family that are involved in regulating the organization of the actin cytoskeleton...
  11. 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...
  12. 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...
  13. 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...
  14. ncbi Cyk3, a novel SH3-domain protein, affects cytokinesis in yeast
    W S Korinek
    Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA
    Curr Biol 10:947-50. 2000
    ..Thus, Cyk3 appears to be important for cytokinesis and acts potentially downstream of Iqg1...
  15. 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...
  16. ncbi Processive phosphorylation of p130Cas by Src depends on SH3-polyproline interactions
    P Pellicena
    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 276:28190-6. 2001
    ..Second, this region aids in anchoring the kinase to Cas to facilitate processive phosphorylation of the substrate domain. The two processes combine to ensure phosphorylation of Cas with high efficiency...
  17. pmc Mammalian Pragmin regulates Src family kinases via the Glu-Pro-Ile-Tyr-Ala (EPIYA) motif that is exploited by bacterial effectors
    Fatemeh Safari
    Division of Microbiology, Graduate School of Medicine, University of Tokyo, Tokyo 113 0033, Japan
    Proc Natl Acad Sci U S A 108:14938-43. 2011
    ..This work identifies Pragmin as a mammalian EPIYA effector and suggests that bacterial EPIYA effectors target Pragmin to subvert SFKs for successful infection...
  18. ncbi SH3 domains from a subset of BAR proteins define a Ubl-binding domain and implicate parkin in synaptic ubiquitination
    Jean Francois Trempe
    Department of Biochemistry, McGill University, Montreal, Quebec, Canada
    Mol Cell 36:1034-47. 2009
    ..The findings identify a pathway for the recruitment of synaptic substrates to parkin with the potential to explain the defects in synaptic transmission observed in recessive forms of PD...
  19. 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...
  20. 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
    ....
  21. 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...
  22. 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...
  23. 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...
  24. pmc Mammalian Abp1, a signal-responsive F-actin-binding protein, links the actin cytoskeleton to endocytosis via the GTPase dynamin
    M M Kessels
    Department of Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology, D 39008 Magdeburg, Germany
    J Cell Biol 153:351-66. 2001
    ....
  25. ncbi Interaction of Bnr1p with a novel Src homology 3 domain-containing Hof1p. Implication in cytokinesis in Saccharomyces cerevisiae
    T Kamei
    Department of Molecular Biology and Biochemistry, Osaka University Medical School, Suita 565 0871, Osaka, Japan
    J Biol Chem 273:28341-5. 1998
    ..These results indicate that Bnr1p directly interacts with Hof1p as well as with profilin to regulate cytoskeletal functions in S. cerevisiae...
  26. ncbi Crystal structure of the conserved core of HIV-1 Nef complexed with a Src family SH3 domain
    C H Lee
    The Rockefeller University, New York, New York 10021, USA
    Cell 85:931-42. 1996
    ..The Nef-SH3 structure also reveals how high affinity and specificity in the SH3 interaction is achieved by the presentation of the PxxP motif within the context of the folded structure of Nef...
  27. ncbi 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...
  28. 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...
  29. 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...
  30. 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...
  31. 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...
  32. 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...
  33. pmc Association of mouse actin-binding protein 1 (mAbp1/SH3P7), an Src kinase target, with dynamic regions of the cortical actin cytoskeleton in response to Rac1 activation
    M M Kessels
    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720 3202, USA
    Mol Biol Cell 11:393-412. 2000
    ..mAbp1 is a newly identified cytoskeletal protein in mice and may serve as a signal-responsive link between the dynamic cortical actin cytoskeleton and regions of membrane dynamics...
  34. ncbi Structure and function analysis of the CMS/CIN85 protein family identifies actin-bundling properties and heterotypic-complex formation
    Gabriel Gaidos
    Department of Biochemistry, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118, USA
    J Cell Sci 120:2366-77. 2007
    ....
  35. ncbi The structure of SOCS3 reveals the basis of the extended SH2 domain function and identifies an unstructured insertion that regulates stability
    Jeffrey J Babon
    The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, 3050, Victoria, Australia
    Mol Cell 22:205-16. 2006
    ..The PEST motif increases SOCS3 turnover and affects its degradation pathway, implying that it has an important regulatory role inside the cell...
  36. pmc Association of the adaptor molecule LAT with CD4 and CD8 coreceptors identifies a new coreceptor function in T cell receptor signal transduction
    R Bosselut
    Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Exp Med 190:1517-26. 1999
    ..These results point to a new function for CD4 and CD8 coreceptors in TCR signal transduction, namely to promote LAT phosphorylation by ZAP-70 by recruiting LAT to major histocompatibility complex-engaged TCR complexes...
  37. ncbi Obligatory steps in protein folding and the conformational diversity of the transition state
    J C Martinez
    EMBL, Heidelberg, Germany
    Nat Struct Biol 5:721-9. 1998
    ....
  38. pmc Mutational analyses of the SOCS proteins suggest a dual domain requirement but distinct mechanisms for inhibition of LIF and IL-6 signal transduction
    S E Nicholson
    The Walter and Eliza Hall Institute of Medical Research and the Cooperative Research Center for Cellular Growth Factors, Parkville, Victoria 3050, Australia
    EMBO J 18:375-85. 1999
    ..Thus, although inhibition of signaling by SOCS-1 and SOCS-3 requires both the SH2 and N-terminal domains, their mechanisms of action appear to be biochemically different...
  39. 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...
  40. pmc Targeting the SH2-kinase interface in Bcr-Abl inhibits leukemogenesis
    Florian Grebien
    Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
    Cell 147:306-19. 2011
    ..This work validates the SH2-kinase interface as an allosteric target for therapeutic intervention...
  41. ncbi SH3 domain ligand binding: What's the consensus and where's the specificity?
    Kalle Saksela
    Department of Virology, Haartman Institute, University of Helsinki and HUSLAB, University of Helsinki Central Hospital, FI 00014 Helsinki, Finland
    FEBS Lett 586:2609-14. 2012
    ..Here we discuss the structural basis of non-consensus SH3 ligand binding and the dominant role of the SH3 domain specificity zone in selective target recognition, and review some of the best-characterized examples of such interactions...
  42. 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...
  43. ncbi Adaptor protein Nck1 interacts with p120 Ras GTPase-activating protein and regulates its activity
    Marija Ger
    Proteomics Centre, Vilnius University Institute of Biochemistry, Lithuania
    Cell Signal 23:1651-8. 2011
    ..This leads to the complex dissipation, decrease of RasGAP activity and the increase of H-Ras-GTP level in the detached cells. Our findings reveal unexpected feature of adaptor protein Nck1 as the regulator of RasGAP activity...
  44. 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...
  45. 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...
  46. 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...
  47. 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...
  48. 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...
  49. ncbi 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...
  50. 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...
  51. 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...
  52. 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...
  53. 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...
  54. 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...
  55. 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...
  56. 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...
  57. 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...
  58. ncbi 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
    ....
  59. pmc An SH3 domain-containing GTPase-activating protein for Rho and Cdc42 associates with focal adhesion kinase
    J D Hildebrand
    Department of Microbiology, Health Sciences Center, University of Virginia, Charlottesville 22908, USA
    Mol Cell Biol 16:3169-78. 1996
    ..We suggest that Graf may function to mediate cross talk between the tyrosine kinases such as FAK and the Rho family GTPase that control steps in integrin-initiated signaling events...
  60. 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...
  61. ncbi Structural basis for the autoinhibition of c-Abl tyrosine kinase
    Bhushan Nagar
    Howard Hughes Medical Institute and Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA
    Cell 112:859-71. 2003
    ....
  62. ncbi The Nck family of adapter proteins: regulators of actin cytoskeleton
    Laszlo Buday
    Department of Medical Chemistry, Semmelweis University Medical School, 9 Puskin Str, 1088, Budapest, Hungary
    Cell Signal 14:723-31. 2002
    ..The proteins of Nck family are implicated in organisation of actin cytoskeleton, cell movement or axon guidance in flies. In this review, the author attempts to summarise signalling pathways in which Nck plays a critical role...
  63. pmc Protein tyrosine phosphatase-PEST regulates focal adhesion disassembly, migration, and cytokinesis in fibroblasts
    A Angers-Loustau
    Department of Biochemistry, McGill University, Montreal, Quebec, Canada H3G 1Y6
    J Cell Biol 144:1019-31. 1999
    ....
  64. doi Discovery of chromone-based inhibitors of the transcription factor STAT5
    Judith Müller
    Max Planck Institute of Biochemistry, Department of Molecular Biology, Am Klopferspitz 18, 82152 Martinsried, Germany
    Chembiochem 9:723-7. 2008
  65. pmc Structural basis for the interaction of the free SH2 domain EAT-2 with SLAM receptors in hematopoietic cells
    M Morra
    Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
    EMBO J 20:5840-52. 2001
    ..We conclude that EAT-2 plays a role in controlling signal transduction through at least four receptors expressed on the surface of professional antigen-presenting cells...
  66. ncbi A family of proteins that inhibit signalling through tyrosine kinase receptors
    A Kharitonenkov
    Department of Molecular Biology, Max Planck Institute für Biochemie, Martinsried, Germany
    Nature 386:181-6. 1997
    ..Our findings indicate that proteins belonging to the SIRP family generally regulate signals defining different physiological and pathological processes...
  67. ncbi Sorting nexin 9 participates in clathrin-mediated endocytosis through interactions with the core components
    Richard Lundmark
    Department of Medical Biochemistry and Biophysics, Umea University, S 901 87 Umea, Sweden
    J Biol Chem 278:46772-81. 2003
    ..Overexpression in both K562 and HeLa cells of truncated forms of SNX9 interfered with the uptake of transferrin, consistent with a role of SNX9 in endocytosis...
  68. pmc The JAK-binding protein JAB inhibits Janus tyrosine kinase activity through binding in the activation loop
    H Yasukawa
    Institute of Life Science, Kurume University, Aikawa machi 2432 3 Kurume 839 0861, Japan
    EMBO J 18:1309-20. 1999
    ..Our studies define a novel type of regulation of tyrosine kinases and might provide a basis for the design of specific tyrosine kinase inhibitors...
  69. pmc Interaction between PAK and nck: a template for Nck targets and role of PAK autophosphorylation
    Z S Zhao
    Glaxo IMCB Group, Institute of Molecular and Cell Biology, Singapore 117609, Singapore
    Mol Cell Biol 20:3906-17. 2000
    ..One cellular consequence of the regulatable binding of PAK is facilitation of its cycling between cytosolic and focal complex sites...
  70. 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...
  71. 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
  72. 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...
  73. 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...
  74. 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...
  75. ncbi 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...
  76. 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...
  77. 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...
  78. 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...
  79. 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...
  80. 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...
  81. 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...
  82. 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...
  83. 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...
  84. 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...
  85. 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...
  86. 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...
  87. pmc Relaxation dispersion NMR spectroscopy as a tool for detailed studies of protein folding
    Philipp Neudecker
    Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada
    Biophys J 96:2045-54. 2009
    ..We review the concerted application of a variety of recently developed NMR relaxation dispersion experiments to obtain a "high-resolution" picture of the folding pathway of the A39V/N53P/V55L Fyn SH3 domain...
  88. 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...
  89. 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...
  90. 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...
  91. ncbi SOCS/CIS protein inhibition of growth hormone-stimulated STAT5 signaling by multiple mechanisms
    P A Ram
    Department of Biology, Division of Cell Biology, Boston University, Boston, Massachusetts 02215, USA
    J Biol Chem 274:35553-61. 1999
    ....
  92. pmc Multiple stimuli induce tyrosine phosphorylation of the Crk-binding sites of paxillin
    M D Schaller
    Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill, NC 27599, USA
    Biochem J 360:57-66. 2001
    ..Thus multiple stimuli may elicit similar signalling events downstream of paxillin...
  93. ncbi The WW domain: linking cell signalling to the membrane cytoskeleton
    Jane L Ilsley
    IBLS, Glasgow Cell Biology Group, Division of Biochemistry and Molecular Biology, University of Glasgow, G12 8QQ, Glasgow, UK
    Cell Signal 14:183-9. 2002
    ....
  94. 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...
  95. 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...
  96. ncbi 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...
  97. 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...
  98. 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...
  99. 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...
  100. 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...
  101. 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...

Research Grants64

  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. 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. ..
  4. The Promoter or A Prostate Specific Gene, Cten
    SU LO; Fiscal Year: 2004
    ....
  5. T Cell Responsiveness and Homeostasis in Anti-Tumor
    Thomas F Gajewski; Fiscal Year: 2010
    ..T cell transduction and tumor transfectants will be examined using factors identified to be useful from the TCR Tg model and mechanisms of improved tumor control will be dissected. ..
  6. Mechanism of RIN1 Signaling in Neuronal Plasticity
    John Colicelli; Fiscal Year: 2007
    ..Special focus will be placed on dendritic spine remodeling because the connection of this phenomenon to learning remains conjectural. [unreadable] [unreadable]..
  7. A Growth-Regulating Protein Tyrosine Phosphatase
    Jonathan Chernoff; Fiscal Year: 2007
    ..Importantly, it also may point the way to the development of new therapeutic agents for diseases such as diabetes and cancer. ..
  8. Mechanistic aspects of integrin-mediated Yersinia uptake
    Amy Bouton; Fiscal Year: 2007
    ..abstract_text> ..
  9. Functions of Drosophila phosphatases Pez and Meg
    Kevin Edwards; Fiscal Year: 2007
    ..Failure to regulate this system leads to metastatic cancer, diabetes, and other diseases. [unreadable] [unreadable] [unreadable]..
  10. Cytokine Signaling in Glioblastoma Cells
    SAIKH HAQUE; Fiscal Year: 2007
    ..abstract_text> ..
  11. Rim and Exocytosis in Chromaffin Cells
    RONALD HOLZ; Fiscal Year: 2006
    ..Experiments with cultures of hippocampal neurons will investigate the roles of the Rim/Rab3a interaction and of the Rim1 PDZ domain in the localization of transfected Rim1 in nerve terminals. ..
  12. PP4 and IGF-1 Signaling in Breast Tumorigenesis
    Tse Hua Tan; Fiscal Year: 2006
    ..These studies will provide new insight into the novel regulation of IGF-1 signaling by PP4 in breast cancer. Furthermore, this study may lead to the identification of PP4 as a novel target for breast cancer therapeutics. ..
  13. YopT: A Yersinia Virulence Factor
    Jack Dixon; Fiscal Year: 2006
    ..In addition, even though we have determined the structure of a YopT family member, AvrPphB, it will be essential to have a structure of YopT in order to identify potential inhibitors directed against this protease. ..
  14. Protein Phosphatases and Proinflammatory Cytokines
    Tse Hua Tan; Fiscal Year: 2006
    ....
  15. HPK1-Mediated Lymphocyte Signal Transduction Mechanisms
    Tse Hua Tan; Fiscal Year: 2005
    ..AIM 2. Study in vivo functions of HPK1 in T-cell mediated immune responses, autoimmunity, and antigen-presenting cell (APC) function using HPK1 knockout mice. ..
  16. Interactions between CLIP-170 and tubulin
    Holly Goodson; Fiscal Year: 2007
    ..abstract_text> ..
  17. Molecular Regulation and Celluar Signaling of Lrrk2 in Parkinson's Disease
    Kathleen Gallo; Fiscal Year: 2007
    ....
  18. Ras signaling in leukemogenesis
    Ruibao Ren; Fiscal Year: 2010
    ..The ultimate goal of these studies is to identify critical molecular events in Ras leukemogenesis, allowing therapeutic interventions of leukemias involving Ras. ..
  19. The Plasma Membrane-Granule Interface in Exocytosis
    Ronald W Holz; Fiscal Year: 2010
    ..The results will be of fundamental importance in the understanding of neurological, endocrine and cardiovascular systems in health and disease. ..
  20. Protein Phosphatases in Lymphocyte Signal Transduction
    Tse Hua Tan; Fiscal Year: 2009
    ..Aim 2. Study in vivo functions of PP4 in T-cell mediated immune responses and autoimmunity using Tcell specific PP4 conditional knockout mice. ..
  21. Zebrafish Protein & Antibody Core
    Brian Kay; Fiscal Year: 2008
    ..We propose a sharing plan consisting of a website containing publicly accessible data, presentations at scientific meetings, and distribution of requested reagents and protocols. [unreadable] [unreadable] [unreadable]..
  22. Role of Dystroglycan in Prostate Function and Regeneration
    Michael Henry; Fiscal Year: 2008
    ..This work is relevant to understanding how disruption of the normal biology if the prostate lead to diseases such as prostate cancer. [unreadable] [unreadable] [unreadable]..
  23. Antitumor Mechanisms of SRC Inhibitors in Lung Cancer
    Eric Haura; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  24. Mechanism of PTK Substrate Recognition and Specificity
    Gongqin Sun; Fiscal Year: 2008
    ..This work will not only reveal detailed information as to how Csk recognizes Src, but may also provide the basis for a general model of PTK substrate specificity and a new paradigm for PTK inhibitor design. [unreadable] [unreadable]..
  25. Molecular Mechanism of Pathogenesis
    Jack Dixon; Fiscal Year: 2008
    ..Finally, we propose to obtain the x-ray structure of AvrPphB complexed with a peptide substrate. These experiments will provide us with new insights into the molecular mechanism of pathogenesis. [unreadable] [unreadable]..
  26. PROTEIN TYROSINE DEPHOSPHORYLATION & SIGNAL TRANSDUCTION
    Nicholas Tonks; Fiscal Year: 2008
    ..Furthermore, proteomics-based strategies are being developed for PTP identification in biological samples, to define novel therapeutic targets for human disease. ..
  27. The role of s-SHIP in normal and tumorigenic development of the skin
    LARRY ROHRSCHNEIDER; Fiscal Year: 2007
    ..Relevance: The research in this proposal is aimed at understanding the expression and function of a single protein which may be critical for the development of the epidermis. [unreadable] [unreadable] [unreadable]..
  28. 2004 Growth Factor Signalling Gordon Conference
    Michael Yaffe; Fiscal Year: 2008
    ..abstract_text> ..
  29. Identification of Molecular Pathways in Cancer Biology
    Michael Yaffe; Fiscal Year: 2005
    ..abstract_text> ..
  30. Regulation of STAT Activity by Tyrosine Phosphatases
    Ke Shuai; Fiscal Year: 2005
    ..We will test the hypothesis that TC45 has intrinsic substrate specificity toward STATs by biochemical assays and domain-swapping analysis. The dephosphorylation of other STATs will be examined. ..
  31. NEGATIVE REGULATION OF INTERLEUKIN-4 SIGNALING
    SAIKH HAQUE; Fiscal Year: 2004
    ..abstract_text> ..
  32. Technologies To Block Gene Expression in Normal T Cells
    Thomas Gajewski; Fiscal Year: 2003
    ..abstract_text> ..
  33. EFFECTORS AND REGULATORS OF NORMAL AND ONCOGENIC RAS
    John Colicelli; Fiscal Year: 2002
    ..These studies, directed at the role of Rin1 function in Ras-mediated signal transduction, should facilitate their understanding of normal cellular processes including differentiation and mitosis as well as cancer pathologies. ..
  34. STRUCTURAL STUDIES OF DNA REPLICATION AND REPAIR
    Gabriel Waksman; Fiscal Year: 2003
    ..Such structures will provide information on the mechanism of active unwinding by DNA-helicases and of passive unwinding by helix-destabilizing SSB proteins. ..
  35. REGULATION OF IMMUNOGLOBULIN GENE EXPRESSION IN B CELLS
    Ruibao Ren; Fiscal Year: 2003
    ..The rules of combinatorial transcription activation will also allow the design of novel transcription regulatory sequences to direct therapeutic expression of exogenous genes in selected cells. ..
  36. SHIP PROTEINS AND SIGNAL TRANSDUCTION
    LARRY ROHRSCHNEIDER; Fiscal Year: 2003
    ..abstract_text> ..
  37. PHOSPHATIDYLINOSITOL 3 KINASE IN B CELL ACTIVATION
    KENNETH COGGESHALL; Fiscal Year: 2003
    ..Such information may reveal novel therapeutic targets in a variety of pathologic conditions and contribute to the etiology of such diseases. ..
  38. P56C2, A NOVEL C2 DOMAIN PROTEIN OF LEUKOCYTES
    BERNARD BABIOR; Fiscal Year: 2003
    ..abstract_text> ..
  39. INHIBITION OF CYTOKINE SIGNALING BY PIS PROTEINS
    Ke Shuai; Fiscal Year: 2002
    ....
  40. IMMUNOREGULATORY DEFECTS IN HEMOPHILIA
    John Sullivan; Fiscal Year: 2001
    ..These studies should further our understanding of HIV-1 specific cell-mediated immunity and provide new information which will be useful in the development of an effective vaccine for the prevention of HIV-1 infection. ..
  41. DEVELOPING A POTENT INHIBITOR OF HIV-I INTEGRASE
    Naijie Jing; Fiscal Year: 2001
    ....
  42. Confocal Live Cell Imaging Instrument
    WILLIAM KINSEY; Fiscal Year: 2004
    ..He will also study calcium transients in granulosa cells induced to divide in vitro with tumor necrosis factor alpha. ..
  43. NEUTROPHIL ACTIVATION OF THE OXIDATIVE BURST
    Robert Clark; Fiscal Year: 2004
    ..non-myeloid tissues and the response to inflammatory stimuli and cell maturation. ..
  44. Molecular Dissection of T Cell Anergy
    Thomas Gajewski; Fiscal Year: 2005
    ..Ultimately, a complete understanding of the anergic state on the molecular level should guide the development of novel pharmacologic therapies to promote or reverse peripheral tolerance in vivo. ..
  45. High-Throughput Assay Design:Polo Kinase Inhibitors(RMI)
    Michael Yaffe; Fiscal Year: 2004
    ..The development of these assays should allow rapid screening of small molecule Polo kinase inhibitors that will function as novel anti-cancer agents. ..
  46. NCRR Shared Instrumentation Grant (SIG) Program
    Michael Yaffe; Fiscal Year: 2005
    ..abstract_text> ..
  47. Biochemical/Molecular Changes Upon Naive T Cell Priming
    Thomas Gajewski; Fiscal Year: 2005
    ....
  48. CSF-1 RECEPTOR SIGNALLING AND G1 PROGRESSION
    Martine Roussel; Fiscal Year: 2001
    ..The identification of novel effector molecules should enable definition of regulatory networks that govern events late in G1 phase, including the commitment to enter S phase. ..
  49. HGF Signaling in Pulmonary Remodeling
    Regina Day; Fiscal Year: 2007
    ..In addition, it is expected that the results will fundamentally advance the field of lung cell biology. ..
  50. Nuclear Factor Kappa B activation by NADPH Oxidases
    Robert Clark; Fiscal Year: 2004
    ..Collectively, these studies will establish a scientific basis for the potential role in aging of the activation of NF-KB by the products of NADPH oxidases of phagocytic and non-phagocytic cells. ..
  51. EXPANSION AND CENTRALIZATION OF AQUATIC ANIMAL HOUSING
    John Sullivan; Fiscal Year: 2004
    ..The requested basic research equipment will be used by both zebrafish and Xenopus users and will significantly augment UMMS aquatic animal research. ..
  52. Quality Improvement through Electronic Enhancements
    John Sullivan; Fiscal Year: 2003
    ..abstract_text> ..
  53. Regulation of Cytokine Signaling by PIAS Protein
    Ke Shuai; Fiscal Year: 2004
    ..These studies will provide important information on the understanding of the cytokine-triggered gene activation pathways and will enhance our ability to design rational therapeutic strategies employing cytokines. ..
  54. REGULATION OF P21-ACTIVATED KINASES
    Jonathan Chernoff; Fiscal Year: 2004
    ..Understanding the molecular basis for this regulation is not only of intrinsic scientific interest but is also likely to be relevant to important human diseases such as metastatic cancer. ..
  55. York College MARC U-STAR Program
    Ruel Desamero; Fiscal Year: 2008
    ..The trainee will also attend professional meetings in his/her discipline, present posters and make oral presentations. [unreadable] [unreadable] [unreadable]..
  56. 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. ..
  57. Docking protein FRS2 in FGF signaling
    Joseph Schlessinger; Fiscal Year: 2008
    ..abstract_text> ..
  58. 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. ..
  59. INTERLEUKIN 6 AND HUMAN BILIARY EPITHELIAL PROLIFERATION
    Anthony Demetris; Fiscal Year: 2006
    ..abstract_text> ..
  60. 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. [unreadable] [unreadable] [unreadable]..
  61. Protein Packing Defects as Functional Markers and Drug Targets
    Ariel Fernandez; Fiscal Year: 2008
    ..Thus, the novel design concept of "drug inhibitor as a wrapper of functional packing defects" will be explored and validated. ..