Tony Pawson

Summary

Affiliation: Samuel Lunenfeld Research Institute
Country: Canada

Publications

  1. ncbi request reprint Dynamic control of signaling by modular adaptor proteins
    Tony Pawson
    Samuel Lunenfeld Research Institute, Mt Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada
    Curr Opin Cell Biol 19:112-6. 2007
  2. pmc Cytokine signaling and hematopoietic homeostasis are disrupted in Lnk-deficient mice
    Laura Velazquez
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada
    J Exp Med 195:1599-611. 2002
  3. pmc Role of p120 Ras-GAP in directed cell movement
    S V Kulkarni
    Programme in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada, M5G 1X5
    J Cell Biol 149:457-70. 2000
  4. pmc Structural coupling of SH2-kinase domains links Fes and Abl substrate recognition and kinase activation
    Panagis Filippakopoulos
    Structural Genomics Consortium, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, UK
    Cell 134:793-803. 2008
  5. pmc PreBIND and Textomy--mining the biomedical literature for protein-protein interactions using a support vector machine
    Ian Donaldson
    Samuel Lunenfeld Research Institute, Toronto, M5G 1X5, Canada
    BMC Bioinformatics 4:11. 2003
  6. pmc Analysis of a Shc family adaptor protein, ShcD/Shc4, that associates with muscle-specific kinase
    Nina Jones
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario, Canada
    Mol Cell Biol 27:4759-73. 2007
  7. ncbi request reprint Organization of cell-regulatory systems through modular-protein-interaction domains
    Tony Pawson
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada
    Philos Trans A Math Phys Eng Sci 361:1251-62. 2003
  8. ncbi request reprint Characterization of the phosphotyrosine-binding domain of the Drosophila Shc protein
    S C Li
    Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada
    J Biol Chem 271:31855-62. 1996
  9. ncbi request reprint 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
  10. ncbi request reprint Protein-protein interactions define specificity in signal transduction
    T Pawson
    Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mt Sinai Hospital, Toronto, Ontario M5G 1X5, Canada
    Genes Dev 14:1027-47. 2000

Detail Information

Publications168 found, 100 shown here

  1. ncbi request reprint Dynamic control of signaling by modular adaptor proteins
    Tony Pawson
    Samuel Lunenfeld Research Institute, Mt Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada
    Curr Opin Cell Biol 19:112-6. 2007
    ..Adaptors can also control the oligomerization of receptor signaling complexes, and the subcellular location and duration of signaling events, and act as coincidence detectors to enhance specificity in cellular responses...
  2. pmc Cytokine signaling and hematopoietic homeostasis are disrupted in Lnk-deficient mice
    Laura Velazquez
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada
    J Exp Med 195:1599-611. 2002
    ..These data implicate Lnk as playing an important role in hematopoiesis and in the regulation of growth factor and cytokine receptor-mediated signaling...
  3. pmc Role of p120 Ras-GAP in directed cell movement
    S V Kulkarni
    Programme in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada, M5G 1X5
    J Cell Biol 149:457-70. 2000
    ..This observation suggests a specific function for Ras-GAP separate from Ras regulation in cell motility...
  4. pmc Structural coupling of SH2-kinase domains links Fes and Abl substrate recognition and kinase activation
    Panagis Filippakopoulos
    Structural Genomics Consortium, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, UK
    Cell 134:793-803. 2008
    ..Thus, the SH2 and catalytic domains of active Fes and Abl pro-oncogenic kinases form integrated structures essential for effective tyrosine kinase signaling...
  5. pmc PreBIND and Textomy--mining the biomedical literature for protein-protein interactions using a support vector machine
    Ian Donaldson
    Samuel Lunenfeld Research Institute, Toronto, M5G 1X5, Canada
    BMC Bioinformatics 4:11. 2003
    ..We present an information extraction system that was designed to locate protein-protein interaction data in the literature and present these data to curators and the public for review and entry into BIND...
  6. pmc Analysis of a Shc family adaptor protein, ShcD/Shc4, that associates with muscle-specific kinase
    Nina Jones
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario, Canada
    Mol Cell Biol 27:4759-73. 2007
    ..Thus, we have characterized a new member of the Shc family of docking proteins, which may mediate a specific aspect of signaling downstream of the MuSK receptor...
  7. ncbi request reprint Organization of cell-regulatory systems through modular-protein-interaction domains
    Tony Pawson
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada
    Philos Trans A Math Phys Eng Sci 361:1251-62. 2003
    ..Cell regulatory proteins have a modular architecture, which may have facilitated the evolution of new signalling pathways, and is exploited by pathogenic micro-organisms and chimeric oncoproteins to re-specify cellular function...
  8. ncbi request reprint Characterization of the phosphotyrosine-binding domain of the Drosophila Shc protein
    S C Li
    Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada
    J Biol Chem 271:31855-62. 1996
    ..The invertebrate dShc PTB domain therefore possesses a binding specificity for tyrosine-phosphorylated peptides that is optimally suited for recognition of the activated DER receptor...
  9. ncbi request reprint 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...
  10. ncbi request reprint Protein-protein interactions define specificity in signal transduction
    T Pawson
    Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mt Sinai Hospital, Toronto, Ontario M5G 1X5, Canada
    Genes Dev 14:1027-47. 2000
  11. ncbi request reprint Synthetic modular systems--reverse engineering of signal transduction
    Tony Pawson
    Samuel Lunenfeld Research Institute, Mt Sinai Hospital, 600 University Avenue, Toronto, ON, Canada M5G 1X5
    FEBS Lett 579:1808-14. 2005
    ..Designing and successfully introducing synthetic proteins into cellular pathways would provide us with a powerful research tool with many applications, such as development of biosensors, protein drugs and rewiring of biological pathways...
  12. ncbi request reprint Oncogenic re-wiring of cellular signaling pathways
    T Pawson
    Centre for Systems Biology, Samuel Lunenfeld Research Institute, Mt Sinai Hospital, 600 University Avenue, Toronto, Ontario, Canada
    Oncogene 26:1268-75. 2007
    ..Compounds that directly or indirectly reverse these aberrant interactions offer new possibilities for therapy in cancer...
  13. ncbi request reprint 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...
  14. ncbi request reprint Assembly of cell regulatory systems through protein interaction domains
    Tony Pawson
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada
    Science 300:445-52. 2003
    ..The fundamental properties of protein interaction domains are discussed in this review and in detailed reviews on individual domains at Science's STKE at http://www.sciencemag.org/cgi/content/full/300/5618/445/DC1...
  15. ncbi request reprint 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...
  16. ncbi request reprint Regulation and targets of receptor tyrosine kinases
    Tony Pawson
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ont M5G 1X5, Canada
    Eur J Cancer 38:S3-10. 2002
    ..Mutations in the juxtamembrane region of several RTKs have been shown to play a role in oncogenesis. It is likely that dysregulation of other modular components of signaling pathways also plays a role in oncogenic transformation...
  17. doi request reprint Network medicine
    Tony Pawson
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Canada
    FEBS Lett 582:1266-70. 2008
    ..We term this approach, network medicine...
  18. 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...
  19. ncbi request reprint The K15 protein of Kaposi's sarcoma-associated herpesvirus recruits the endocytic regulator intersectin 2 through a selective SH3 domain interaction
    Caesar S Lim
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada
    Biochemistry 46:9874-85. 2007
    ..The ability of K15 to associate with ITSN2 suggests a new role for the K15 viral protein in intracellular protein trafficking...
  20. pmc Systematic discovery of in vivo phosphorylation networks
    Rune Linding
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada
    Cell 129:1415-26. 2007
    ..Applying this approach to DNA damage signaling, we show that 53BP1 and Rad50 are phosphorylated by CDK1 and ATM, respectively. We describe a scalable strategy to evaluate predictions, which suggests that BCLAF1 is a GSK-3 substrate...
  21. doi request reprint Structural studies of FF domains of the transcription factor CA150 provide insights into the organization of FF domain tandem arrays
    James M Murphy
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
    J Mol Biol 393:409-24. 2009
    ....
  22. pmc Nck adaptor proteins control the organization of neuronal circuits important for walking
    James P Fawcett
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, Canada
    Proc Natl Acad Sci U S A 104:20973-8. 2007
    ..Our data indicate that Nck adaptors couple pTyr guidance signals to cytoskeletal events required for the ipsilateral projections of spinal cord neurons and thus for normal limb movement...
  23. ncbi request reprint Comparative analysis reveals conserved protein phosphorylation networks implicated in multiple diseases
    Chris Soon Heng Tan
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5
    Sci Signal 2:ra39. 2009
    ..We reveal that multiple complex diseases seem to converge within the conserved networks, suggesting that disease development might rely on common molecular networks...
  24. pmc Screening for PTB domain binding partners and ligand specificity using proteome-derived NPXY peptide arrays
    Matthew J Smith
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5
    Mol Cell Biol 26:8461-74. 2006
    ..Proteome-based peptide arrays can therefore identify networks of receptor interactions with scaffold proteins that may be physiologically relevant...
  25. pmc WW domains provide a platform for the assembly of multiprotein networks
    Robert J Ingham
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
    Mol Cell Biol 25:7092-106. 2005
    ..These data suggest that WW domains provide a versatile platform to link individual proteins into physiologically important networks...
  26. ncbi request reprint A Rich1/Amot complex regulates the Cdc42 GTPase and apical-polarity proteins in epithelial cells
    Clark D Wells
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada
    Cell 125:535-48. 2006
    ..We propose that Rich1 and Amot maintain TJ integrity by the coordinate regulation of Cdc42 and by linking specific components of the TJ to intracellular protein trafficking...
  27. doi request reprint Analysis of EphA4 receptor tyrosine kinase substrate specificity using peptide-based arrays
    Neil Warner
    Program in Systems Biology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada
    FEBS J 275:2561-73. 2008
    ..Our findings identify several potential EphA4 substrates and demonstrate the general utility of using peptide arrays to rapidly identify and map protein kinase phosphorylation sites...
  28. pmc Composite low affinity interactions dictate recognition of the cyclin-dependent kinase inhibitor Sic1 by the SCFCdc4 ubiquitin ligase
    Xiaojing Tang
    Center for Systems Biology, Samuel Lunenfeld Research Institute, Toronto, ON, Canada M5G 1X5
    Proc Natl Acad Sci U S A 109:3287-92. 2012
    ..Composite dynamic interactions of low affinity sites may be a general mechanism to establish phosphorylation thresholds in biological responses...
  29. pmc UNC-129 regulates the balance between UNC-40 dependent and independent UNC-5 signaling pathways
    Lesley T MacNeil
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada
    Nat Neurosci 12:150-5. 2009
    ..Similar regulatory interactions between oppositely graded extracellular cues may be a common theme in guided cell and axon migrations...
  30. pmc The PTB domain of ShcA couples receptor activation to the cytoskeletal regulator IQGAP1
    Matthew J Smith
    Ontario Cancer Institute, MaRS TMDT, Toronto, Canada
    EMBO J 29:884-96. 2010
    ..ShcA-mediated recruitment of IQGAP1 may have an important role in cytoskeletal reorganization downstream of activated receptors at the cell surface...
  31. ncbi request reprint A global protein kinase and phosphatase interaction network in yeast
    Ashton Breitkreutz
    Centre for Systems Biology, Samuel Lunenfeld Research Institute, 600 University Avenue, Toronto, Ontario, M5G 1X5, Canada
    Science 328:1043-6. 2010
    ..An extensive backbone of kinase-kinase interactions cross-connects the proteome and may serve to coordinate diverse cellular responses...
  32. pmc Efficient T-cell receptor signaling requires a high-affinity interaction between the Gads C-SH3 domain and the SLP-76 RxxK motif
    Bruce T Seet
    Centre for Systems Biology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
    EMBO J 26:678-89. 2007
    ....
  33. doi request reprint Cell-specific information processing in segregating populations of Eph receptor ephrin-expressing cells
    Claus Jørgensen
    Samuel Lunenfeld Research Institute SLRI, Mount Sinai Hospital, Toronto M5G 1X5, Canada
    Science 326:1502-9. 2009
    ..We provide systems- and cell-specific network models of contact-initiated signaling between two distinct cell types...
  34. pmc A change in conformational dynamics underlies the activation of Eph receptor tyrosine kinases
    Silke Wiesner
    Structural Biology and Biochemistry, Hospital for Sick Children, Toronto, Ontario, Canada
    EMBO J 25:4686-96. 2006
    ....
  35. doi request reprint Eukaryotic protein domains as functional units of cellular evolution
    Jing Jin
    Centre for Systems Biology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Ontario, Canada
    Sci Signal 2:ra76. 2009
    ..Based on this scheme, we propose a mechanism by which Tudor domains may have evolved to support different modes of epigenetic regulation and suggest a role for the germline group of mammalian Tudor domains in Piwi-regulated RNA biology...
  36. ncbi request reprint Structural basis for specific binding of the Gads SH3 domain to an RxxK motif-containing SLP-76 peptide: a novel mode of peptide recognition
    Qin Liu
    Department of Biochemistry, Faculty of Medicine and Dentistry, University of Western Ontario, N6A 5C1, London, Ontario, Canada
    Mol Cell 11:471-81. 2003
    ..The structure, and supporting mutagenesis and peptide binding data, reveal a novel mode of ligand recognition by SH3 domains...
  37. pmc Nck proteins maintain the adult glomerular filtration barrier
    Nina Jones
    Department of Molecular and Cellular Biology, University of Guelph, 50 Stone Road East, New Science Complex, Guelph, Ontario, Canada
    J Am Soc Nephrol 20:1533-43. 2009
    ..These data suggest that Nck is required to maintain adult podocytes and that phosphotyrosine-based interactions with nephrin may occur in foot processes of resting, mature podocytes...
  38. ncbi request reprint 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...
  39. pmc The UNC-73/Trio RhoGEF-2 domain is required in separate isoforms for the regulation of pharynx pumping and normal neurotransmission in C. elegans
    Robert Steven
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada
    Genes Dev 19:2016-29. 2005
    ....
  40. pmc Positive selection of tyrosine loss in metazoan evolution
    Chris Soon Heng Tan
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto M5G 1X5, Canada
    Science 325:1686-8. 2009
    ..We propose that this phenomenon illustrates genome-wide adaptive evolution to accommodate beneficial genetic perturbation...
  41. ncbi request reprint The mammalian-membrane two-hybrid assay (MaMTH) for probing membrane-protein interactions in human cells
    Julia Petschnigg
    Donnelly Centre, University of Toronto, Toronto, Ontario, Canada
    Nat Methods 11:585-92. 2014
    ..MaMTH is a powerful tool for investigating the dynamic interactomes of human integral membrane proteins. ..
  42. pmc FF domains of CA150 bind transcription and splicing factors through multiple weak interactions
    Matthew J Smith
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Ave, Toronto, Ontario, Canada, M5G 1X5
    Mol Cell Biol 24:9274-85. 2004
    ..We propose that CA150, through the dual recognition of acidic motifs in proteins such as Tat-SF1 and the phosphorylated CTD, could mediate the recruitment of transcription and splicing factors to actively transcribing RNAPII...
  43. pmc The murine Nck SH2/SH3 adaptors are important for the development of mesoderm-derived embryonic structures and for regulating the cellular actin network
    Friedhelm Bladt
    Programme in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada
    Mol Cell Biol 23:4586-97. 2003
    ..These data suggest that the Nck SH2/SH3 adaptors have important functions in the development of mesodermal structures during embryogenesis, potentially linked to a role in cell movement and cytoskeletal organization...
  44. ncbi request reprint A roadmap to generate renewable protein binders to the human proteome
    Karen Colwill
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
    Nat Methods 8:551-8. 2011
    ..We believe that this work serves as a foundation and template for future larger-scale studies to create renewable protein binders...
  45. ncbi request reprint Non-canonical interaction of phosphoinositides with pleckstrin homology domains of Tiam1 and ArhGAP9
    Derek F J Ceccarelli
    Program in Systems Biology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5
    J Biol Chem 282:13864-74. 2007
    ..We posit that the diversity in PI interaction modes displayed by PH domains contributes to their versatility of use in biological systems...
  46. pmc A Drosophila shc gene product is implicated in signaling by the DER receptor tyrosine kinase
    K M Lai
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
    Mol Cell Biol 15:4810-8. 1995
    ....
  47. ncbi request reprint Proteomic, functional, and domain-based analysis of in vivo 14-3-3 binding proteins involved in cytoskeletal regulation and cellular organization
    Jing Jin
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada
    Curr Biol 14:1436-50. 2004
    ..14-3-3 proteins are abundant and conserved polypeptides that mediate the cellular effects of basophilic protein kinases through their ability to bind specific peptide motifs phosphorylated on serine or threonine...
  48. ncbi request reprint A high-affinity Arg-X-X-Lys SH3 binding motif confers specificity for the interaction between Gads and SLP-76 in T cell signaling
    Donna M Berry
    The Arthur and Sonia Labatt, Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, M5G1X8, Ontario, Canada
    Curr Biol 12:1336-41. 2002
    ..These results provide a molecular explanation for the specific role of Gads in T cell receptor signaling, and identify a discrete subclass of SH3 domains whose binding is dependent on a core R-X-X-K motif...
  49. doi request reprint Temporal regulation of EGF signalling networks by the scaffold protein Shc1
    Yong Zheng
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto M5G 1X5, Canada
    Nature 499:166-71. 2013
    ..The Shc1 scaffold therefore directs the temporal flow of signalling information after EGF stimulation. ..
  50. pmc The adaptor protein Grb2 is not essential for the establishment of the glomerular filtration barrier
    Nicolas Bisson
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Joseph and Wolf Lebovic Health Complex, Toronto, Ontario, Canada
    PLoS ONE 7:e50996. 2012
    ....
  51. ncbi request reprint A polarity complex of mPar-6 and atypical PKC binds, phosphorylates and regulates mammalian Lgl
    Pamela J Plant
    Programme in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto M5G 1X5 Canada
    Nat Cell Biol 5:301-8. 2003
    ....
  52. pmc Conformational instability of the MARK3 UBA domain compromises ubiquitin recognition and promotes interaction with the adjacent kinase domain
    James M Murphy
    Centre for Systems Biology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, and Department of Medical Genetics, University of Toronto, ON, Canada M5G 1X5
    Proc Natl Acad Sci U S A 104:14336-41. 2007
    ..These results may be relevant more generally to the 30% of UBA domains that lack significant ubiquitin-binding activity, and they suggest a unique mechanism by which interaction domains may evolve new binding properties...
  53. doi request reprint Interaction domains of Sos1/Grb2 are finely tuned for cooperative control of embryonic stem cell fate
    Greg M Findlay
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada
    Cell 152:1008-20. 2013
    ..This optimized system ensures that PrE lineage commitment occurs in a timely and selective manner during embryogenesis...
  54. ncbi request reprint Early lineage segregation between epiblast and primitive endoderm in mouse blastocysts through the Grb2-MAPK pathway
    Claire Chazaud
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G1X5, Canada
    Dev Cell 10:615-24. 2006
    ..We propose a model in which the ICM develops as a mosaic of EPI and PE progenitors at E3.5, dependent on Grb2-Ras-MAP kinase signaling, followed by later segregation of the progenitors into the appropriate cell layers...
  55. ncbi request reprint Manipulation of EphB2 regulatory motifs and SH2 binding sites switches MAPK signaling and biological activity
    Jiefei Tong
    Programe in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5
    J Biol Chem 278:6111-9. 2003
    ..The behavior of EphB2 variants with mutations in the JM region and kinase domains suggests an intricate pattern of regulation and target recognition by Eph receptors...
  56. pmc Lnk adaptor suppresses radiation resistance and radiation-induced B-cell malignancies by inhibiting IL-11 signaling
    Igal Louria-Hayon
    Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada M5G 1X5
    Proc Natl Acad Sci U S A 110:20599-604. 2013
    ..IL-11 therefore drives a pathway that enhances HSPC radioresistance and radiation-induced B-cell malignancies, but is normally attenuated by the inhibitory adaptor Lnk. ..
  57. pmc Yap- and Cdc42-dependent nephrogenesis and morphogenesis during mouse kidney development
    Antoine Reginensi
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
    PLoS Genet 9:e1003380. 2013
    ..We propose that Yap responds to Cdc42-dependent signals in nephron progenitor cells to activate a genetic program required to shape the functioning nephron...
  58. pmc Modular evolution of phosphorylation-based signalling systems
    Jing Jin
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario, Canada
    Philos Trans R Soc Lond B Biol Sci 367:2540-55. 2012
    ..This review will focus on the modular aspects of signalling networks and the mechanism by which they may have evolved...
  59. pmc Combinatorial ShcA docking interactions support diversity in tissue morphogenesis
    W Rod Hardy
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada
    Science 317:251-6. 2007
    ..Thus, combinatorial differences in ShcA docking interactions may yield multiple signaling mechanisms to support diversity in tissue morphogenesis...
  60. doi request reprint The Hippo pathway regulates Wnt/beta-catenin signaling
    Xaralabos Varelas
    Center for Systems Biology, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada
    Dev Cell 18:579-91. 2010
    ..These results uncover a cytoplasmic function of TAZ in regulating Wnt signaling and highlight the role of the Hippo pathway in coordinating morphogenetic signaling with growth control...
  61. pmc Protein phosphatase 1 regulates the phosphorylation state of the polarity scaffold Par-3
    Andreas Traweger
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada
    Proc Natl Acad Sci U S A 105:10402-7. 2008
    ....
  62. pmc NetworKIN: a resource for exploring cellular phosphorylation networks
    Rune Linding
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada
    Nucleic Acids Res 36:D695-9. 2008
    ..The database currently contains a predicted phosphorylation network with 20,224 site-specific interactions involving 3978 phosphoproteins and 73 human kinases from 20 families...
  63. pmc Mapping differential interactomes by affinity purification coupled with data-independent mass spectrometry acquisition
    Jean Philippe Lambert
    1 Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada 2
    Nat Methods 10:1239-45. 2013
    ..We show that AP-SWATH is a robust label-free approach to characterize such changes and propose a scalable pipeline for systems biology studies. ..
  64. doi request reprint Rapid and sensitive MRM-based mass spectrometry approach for systematically exploring ganglioside-protein interactions
    Ruijun Tian
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada
    Proteomics 13:1334-8. 2013
    ..05. These results show that the described method provides a rapid and high-sensitive approach for systematically measuring ganglioside-protein interactions...
  65. pmc Modification of the Creator recombination system for proteomics applications--improved expression by addition of splice sites
    Karen Colwill
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
    BMC Biotechnol 6:13. 2006
    ..Usability of the Creator system is impacted by the ability to easily manipulate DNA, the number of acceptor vectors for downstream applications, and the level of protein expression from Creator vectors...
  66. pmc Polyelectrostatic interactions of disordered ligands suggest a physical basis for ultrasensitivity
    Mikael Borg
    Department of Biochemistry, Faculty of Medicine, University of Toronto, Toronto, ON, Canada M5S 1A8
    Proc Natl Acad Sci U S A 104:9650-5. 2007
    ..Thus, polyelectrostatic interactions may provide a simple yet powerful framework for understanding the modulation of protein interactions by multiple phosphorylation sites in disordered protein regions...
  67. pmc Identification of residues that control specific binding of the Shc phosphotyrosine-binding domain to phosphotyrosine sites
    P van der Geer
    Programme in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON Canada
    Proc Natl Acad Sci U S A 93:963-8. 1996
    ....
  68. doi request reprint Deciphering arginine methylation: Tudor tells the tale
    Chen Chen
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada
    Nat Rev Mol Cell Biol 12:629-42. 2011
    ..Tudor proteins are now known to be present in PIWI complexes, where they are thought to interact with methylated PIWI proteins and regulate the PIWI-interacting RNA (piRNA) pathway in the germ line...
  69. pmc Mouse Piwi interactome identifies binding mechanism of Tdrkh Tudor domain to arginine methylated Miwi
    Chen Chen
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada M5G 1X5
    Proc Natl Acad Sci U S A 106:20336-41. 2009
    ....
  70. pmc Immature T-cell clustering and efficient differentiation require the polarity protein Scribble
    Kelly A Pike
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada M5G 1X5
    Proc Natl Acad Sci U S A 108:1116-21. 2011
    ..Scribble is therefore a critical contributor to the clustering of immature T cells, an event shown here to be necessary for efficient developmental progression...
  71. ncbi request reprint Reading protein modifications with interaction domains
    Bruce T Seet
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada
    Nat Rev Mol Cell Biol 7:473-83. 2006
    ..We also identify common strategies through which modification-dependent interactions synergize to regulate cell behaviour...
  72. ncbi request reprint The mammalian ShcB and ShcC phosphotyrosine docking proteins function in the maturation of sensory and sympathetic neurons
    R Sakai
    Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, M5G 1X5, Toronto, Ontario, Canada
    Neuron 28:819-33. 2000
    ..The results indicate that these Shc family members possess both unique and overlapping functions in regulating neural development and suggest physiological roles for ShcB/ShcC in TrkA signaling...
  73. pmc ShcA and Grb2 mediate polyoma middle T antigen-induced endothelial transformation and Gab1 tyrosine phosphorylation
    S H Ong
    Programme in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada
    EMBO J 20:6327-36. 2001
    ..Therefore, PymT activation of ShcA-Grb2 signaling is critical for endothelial transformation, and PymT can stimulate Grb2 signaling to both the MAP kinase and PI3K pathways...
  74. pmc Downregulation of the Ras-mitogen-activated protein kinase pathway by the EphB2 receptor tyrosine kinase is required for ephrin-induced neurite retraction
    S Elowe
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada
    Mol Cell Biol 21:7429-41. 2001
    ....
  75. ncbi request reprint 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...
  76. ncbi request reprint A conserved amino-terminal Shc domain binds to phosphotyrosine motifs in activated receptors and phosphopeptides
    P van der Geer
    Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
    Curr Biol 5:404-12. 1995
    ..Shc itself contains an SH2 domain at its carboxyl terminus, but the function of the amino-terminal half of the protein is unknown...
  77. doi request reprint Novel NEDD1 phosphorylation sites regulate γ-tubulin binding and mitotic spindle assembly
    Maria Ana Gomez-Ferreria
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada
    J Cell Sci 125:3745-51. 2012
    ..We also found that CEP192, a centrosomal protein similarly required for spindle formation, associates with NEDD1 and modulates its mitotic phosphorylation. Thus CEP192 may regulate spindle assembly by modulating NEDD1 function...
  78. ncbi request reprint The Epstein-Barr virus protein, latent membrane protein 2A, co-opts tyrosine kinases used by the T cell receptor
    Robert J Ingham
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada
    J Biol Chem 280:34133-42. 2005
    ..Thus, through recruiting tyrosine kinases involved in T cell receptor activation, LMP2A may provide a survival signal for EBV-positive T cell tumors, whereas LMP2A-associated NEDD4 E3 ligases probably titer the strength of this signal...
  79. pmc The ShcA phosphotyrosine docking protein uses distinct mechanisms to regulate myocyte and global heart function
    Rachel D Vanderlaan
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario, Canada
    Circ Res 108:184-93. 2011
    ..Therefore, ShcA could be a potential hub for downstream TK signaling in the myocardium...
  80. doi request reprint Kinome signaling through regulated protein-protein interactions in normal and cancer cells
    Tony Pawson
    Samuel Lunenfeld Research Institute, Mt Sinai Hospital, Toronto, Ontario, Canada
    Curr Opin Cell Biol 21:147-53. 2009
    ....
  81. pmc Juxtamembrane tyrosine residues couple the Eph family receptor EphB2/Nuk to specific SH2 domain proteins in neuronal cells
    S J Holland
    Programme in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
    EMBO J 16:3877-88. 1997
    ..These results identify an EphB2-activated signalling cascade involving proteins that potentially play a role in axonal guidance and control of cytoskeletal architecture...
  82. ncbi request reprint SH2 domain specificity and activity modified by a single residue
    L E Marengere
    Division of Molecular and Developmental Biology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
    Nature 369:502-5. 1994
    ..These results identify a residue that can modify SH2 selectivity, and indicate that the biological activity of an SH2 domain correlates with its binding specificity...
  83. doi request reprint Selected reaction monitoring mass spectrometry reveals the dynamics of signaling through the GRB2 adaptor
    Nicolas Bisson
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Joseph and Wolf Lebovic Health Complex, Toronto, Ontario, Canada
    Nat Biotechnol 29:653-8. 2011
    ..Capturing a key hub protein and dissecting its interactions by SRM should be equally applicable to quantifying signaling dynamics for a range of hubs in protein interaction networks...
  84. doi request reprint Dynamic modularity in protein interaction networks predicts breast cancer outcome
    Ian W Taylor
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Ave, Toronto, Ontario M5G 1X5, Canada
    Nat Biotechnol 27:199-204. 2009
    ..Analysis of two breast cancer patient cohorts revealed that altered modularity of the human interactome may be useful as an indicator of breast cancer prognosis...
  85. pmc Functional analysis of the Caenorhabditis elegans UNC-73B PH domain demonstrates a role in activation of the Rac GTPase in vitro and axon guidance in vivo
    Terrance J Kubiseski
    Samuel Lunenfeld Research Institute of Mt Sinai Hospital, Toronto, Ontario M5G 1X5, Canada
    Mol Cell Biol 23:6823-35. 2003
    ..These results suggest that the UNC-73B PH domain plays distinct roles in targeting and promoting GEF activity towards the Rac GTPase, both of which are important for the directed movements of motorneurons in vivo...
  86. pmc Conformational determinants of phosphotyrosine peptides complexed with the Src SH2 domain
    Joseph Nachman
    Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada
    PLoS ONE 5:e11215. 2010
    ..The information obtained in this work can be used in the design of specific SH2 domain inhibitors...
  87. ncbi request reprint SH2/SH3 adaptor proteins can link tyrosine kinases to a Ste20-related protein kinase, HPK1
    M Anafi
    Programme in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada
    J Biol Chem 272:27804-11. 1997
    ..Such interaction may provide a possible mechanism for cross-talk between distinct biochemical pathways following the activation of tyrosine kinases...
  88. ncbi request reprint The discoidin domain receptor tyrosine kinases are activated by collagen
    W Vogel
    Programme in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
    Mol Cell 1:13-23. 1997
    ..These results suggest that the discoidin-related DDR tyrosine kinases are novel collagen receptors with the potential to control cellular responses to the extracellular matrix...
  89. ncbi request reprint SH3 binding domains in the dopamine D4 receptor
    J Oldenhof
    Department of Pharmacology, Institute of Medical Science, University of Toronto, Ontario, Canada
    Biochemistry 37:15726-36. 1998
    ..The data indicates that the D4 receptor contains SH3 binding sites and that these sites fall within a region involved in the control of receptor internalization...
  90. ncbi request reprint A Drosophila SH2-SH3 adaptor protein implicated in coupling the sevenless tyrosine kinase to an activator of Ras guanine nucleotide exchange, Sos
    J P Olivier
    Division of Molecular and Developmental Biology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
    Cell 73:179-91. 1993
    ..The conservation of these signaling proteins during evolution indicates that this is a general mechanism for linking tyrosine kinases to Ras...
  91. ncbi request reprint The shc adaptor protein forms interdependent phosphotyrosine-mediated protein complexes in mast cells stimulated with interleukin 3
    L Velazquez
    Programme in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
    Blood 96:132-8. 2000
    ..These results indicate that Shc undergoes an interdependent series of pTyr-mediated interactions in IL-3-stimulated mast cells, resulting in the recruitment of proteins that regulate the Ras pathway and phospholipid metabolism...
  92. ncbi request reprint Nuk controls pathfinding of commissural axons in the mammalian central nervous system
    M Henkemeyer
    Programme in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
    Cell 86:35-46. 1996
    ..These results indicate that Nuk, a receptor that binds transmembrane ligands, plays a critical and unique role in the pathfinding of specific axons in the mammalian central nervous system...
  93. ncbi request reprint The SH2 and SH3 domains of mammalian Grb2 couple the EGF receptor to the Ras activator mSos1
    M Rozakis-Adcock
    Division of Molecular and Developmental Biology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
    Nature 363:83-5. 1993
    ..EGF stimulation induces binding of the Grb2-mSos1 complex to the autophosphorylated EGF receptor, and mSos1 phosphorylation. Grb2 therefore appears to link tyrosine kinases to a Ras-GNRP in mammalian cells...
  94. ncbi request reprint UNC-73 activates the Rac GTPase and is required for cell and growth cone migrations in C. elegans
    R Steven
    Samuel Lunenfeld Research Institute of Mt Sinai Hospital, Toronto, Ontario, Canada
    Cell 92:785-95. 1998
    ..Our results suggest that UNC-73 acts cell autonomously in a protein complex to regulate actin dynamics during cell and growth cone migrations...
  95. ncbi request reprint Novel protein-tyrosine kinase cDNAs related to fps/fes and eph cloned using anti-phosphotyrosine antibody
    K Letwin
    Division of Molecular and Developmental Biology, Mt Sinai Hospital Research Institute, Toronto, Ontario, Canada
    Oncogene 3:621-7. 1988
    ..The preferential isolation of cDNAs for previously uncharacterized protein-tyrosine kinases in a screen based on catalytic activity suggests that additional members of the protein-tyrosine kinase family remain to be identified...
  96. ncbi request reprint Transgenic RNA interference in ES cell-derived embryos recapitulates a genetic null phenotype
    Tilo Kunath
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada M5G 1X5
    Nat Biotechnol 21:559-61. 2003
    ..Such embryos, in which endogenous p120-Ras GTPase-activating protein (RasGAP), encoded by Rasa1 (also known as RasGAP), was silenced, had the same phenotype as did the previously reported Rasa1 null mutation...
  97. pmc A "three-pronged" binding mechanism for the SAP/SH2D1A SH2 domain: structural basis and relevance to the XLP syndrome
    Peter M Hwang
    Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada
    EMBO J 21:314-23. 2002
    ..The structures also explain binding defects observed in disease-causing SAP/SH2D1A mutants and suggest that phosphorylation-independent interactions mediated by SAP/SH2D1A likely play an important role in the pathogenesis of XLP...
  98. pmc Structure of a regulatory complex involving the Abl SH3 domain, the Crk SH2 domain, and a Crk-derived phosphopeptide
    Logan W Donaldson
    Department of Molecular and Medical Genetics, University of Toronto, Toronto, ON, Canada M5S 1A8
    Proc Natl Acad Sci U S A 99:14053-8. 2002
    ..This complex between the Abl SH3 domain, Crk SH2 domain, and Crk phosphopeptide is an example of the extremely modular nature of regulatory proteins that provides a rich repertoire of mechanisms for control of biological function...
  99. pmc Targeted mutations of the juxtamembrane tyrosines in the Kit receptor tyrosine kinase selectively affect multiple cell lineages
    Yuki Kimura
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, Canada M5G 1X5
    Proc Natl Acad Sci U S A 101:6015-20. 2004
    ....
  100. ncbi request reprint The Nedd4 family of E3 ubiquitin ligases: functional diversity within a common modular architecture
    Robert J Ingham
    Samuel Lunenfeld Research Institute, Mt Sinai Hospital, Toronto, Ontario, Canada M5G 1X5
    Oncogene 23:1972-84. 2004
    ..In this review we discuss how knowledge of individual domain function has provided insight into the physiological roles of the Nedd4 proteins and describe recent results that suggest discrete functions for individual family members...
  101. ncbi request reprint Immunolocalization of the Nuk receptor tyrosine kinase suggests roles in segmental patterning of the brain and axonogenesis
    M Henkemeyer
    Division of Molecular and Developmental Biology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
    Oncogene 9:1001-14. 1994
    ....