HCK

Summary

Gene Symbol: HCK
Description: HCK proto-oncogene, Src family tyrosine kinase
Alias: JTK9, p59Hck, p61Hck, tyrosine-protein kinase HCK, hematopoietic cell kinase, hemopoietic cell kinase, p59-HCK/p60-HCK
Species: human

Top Publications

  1. ncbi Fusion of azurophil granules with phagosomes and activation of the tyrosine kinase Hck are specifically inhibited during phagocytosis of mycobacteria by human neutrophils
    E N N'Diaye
    Institut de Pharmacologie et de Biologie Structurale Centre National de la Recherche Scientifique, Unité Propre de Recherche 9062, Toulouse, France
    J Immunol 161:4983-91. 1998
  2. pmc The mannose receptor mediates uptake of pathogenic and nonpathogenic mycobacteria and bypasses bactericidal responses in human macrophages
    C Astarie-Dequeker
    Institut de Pharmacologie et de Biologie Structurale, Centre National de la Recherche Scientifique, UPR 9062, 31077 Toulouse, France
    Infect Immun 67:469-77. 1999
  3. ncbi Complement receptor 3 (CD11b/CD18) mediates type I and type II phagocytosis during nonopsonic and opsonic phagocytosis, respectively
    Véronique Le Cabec
    Institut de Pharmacologie et de Biologie Structurale, Centre National de la Recherche Scientifique, Toulouse, France
    J Immunol 169:2003-9. 2002
  4. pmc Cooperative activation of Src family kinases by SH3 and SH2 ligands
    Shalini S Yadav
    Department of Physiology and Biophysics, School of Medicine, Stony Brook University, Stony Brook, NY 11794 8661, USA
    Cancer Lett 257:116-23. 2007
  5. doi Novel fluorescent dyes based on oligopropylamines for the in vivo staining of eukaryotic unicellular algae
    V V Annenkov
    Limnological Institute of Siberian Branch, Russian Academy of Sciences, 660033 Irkutsk, Russia
    Anal Biochem 407:44-51. 2010
  6. pmc Two isoforms of murine hck, generated by utilization of alternative translational initiation codons, exhibit different patterns of subcellular localization
    P Lock
    Ludwig Institute for Cancer Research, Royal Melbourne Hospital, Parkville, Victoria, Australia
    Mol Cell Biol 11:4363-70. 1991
  7. pmc Novel protein-tyrosine kinase gene (hck) preferentially expressed in cells of hematopoietic origin
    S F Ziegler
    Mol Cell Biol 7:2276-85. 1987
  8. pmc Identification of a human gene (HCK) that encodes a protein-tyrosine kinase and is expressed in hemopoietic cells
    N Quintrell
    Mol Cell Biol 7:2267-75. 1987
  9. 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
  10. pmc Myristoylation and differential palmitoylation of the HCK protein-tyrosine kinases govern their attachment to membranes and association with caveolae
    S M Robbins
    Department of Microbiology, University of California, San Francisco 94143 0552, USA
    Mol Cell Biol 15:3507-15. 1995

Research Grants

  1. Src Family Tyrosine Kinases in Tumor Cell Signaling
    THOMAS SMITHGALL; Fiscal Year: 2007
  2. Src Family Kinases as Molecular Targets for HIV/Nef
    THOMAS EDWARD SMITHGALL; Fiscal Year: 2010
  3. Dianne Cox; Fiscal Year: 2014
  4. Complexes of HIV-1 Nef with Src-family Kinases as Therapeutic Targets
    Lori A Emert Sedlak; Fiscal Year: 2010
  5. Structural Biology of HIV Nef-Src Family Kinase Complexes
    THOMAS EDWARD SMITHGALL; Fiscal Year: 2010
  6. Joanne I Yeh; Fiscal Year: 2016
  7. THOMAS EDWARD SMITHGALL; Fiscal Year: 2016
  8. SRC-LIKE KINASES IN INTERLEUKIN-3 RECEPTOR SIGNALING
    Steven Anderson; Fiscal Year: 2001
  9. Arrestin activation probed with mass spectrometry
    Eric Prossnitz; Fiscal Year: 2007
  10. Grant McFadden; Fiscal Year: 2014

Detail Information

Publications197 found, 100 shown here

  1. ncbi Fusion of azurophil granules with phagosomes and activation of the tyrosine kinase Hck are specifically inhibited during phagocytosis of mycobacteria by human neutrophils
    E N N'Diaye
    Institut de Pharmacologie et de Biologie Structurale Centre National de la Recherche Scientifique, Unité Propre de Recherche 9062, Toulouse, France
    J Immunol 161:4983-91. 1998
    ..b>Hck is a Src family tyrosine kinase associated with azurophil granules...
  2. pmc The mannose receptor mediates uptake of pathogenic and nonpathogenic mycobacteria and bypasses bactericidal responses in human macrophages
    C Astarie-Dequeker
    Institut de Pharmacologie et de Biologie Structurale, Centre National de la Recherche Scientifique, UPR 9062, 31077 Toulouse, France
    Infect Immun 67:469-77. 1999
    ..Activation and translocation of Hck, a Src family tyrosine kinase located on lysosomes, has previously been used as a marker of fusion between ..
  3. ncbi Complement receptor 3 (CD11b/CD18) mediates type I and type II phagocytosis during nonopsonic and opsonic phagocytosis, respectively
    Véronique Le Cabec
    Institut de Pharmacologie et de Biologie Structurale, Centre National de la Recherche Scientifique, Toulouse, France
    J Immunol 169:2003-9. 2002
    ..activity; and 3) CR3-mediated phagocytosis of Z depends on the kinase activity of the Src family tyrosine kinase Hck, while OZ internalization does not...
  4. pmc Cooperative activation of Src family kinases by SH3 and SH2 ligands
    Shalini S Yadav
    Department of Physiology and Biophysics, School of Medicine, Stony Brook University, Stony Brook, NY 11794 8661, USA
    Cancer Lett 257:116-23. 2007
    ..Here, we carried out in vitro activation experiments with purified, down-regulated hematopoietic cell kinase (Hck), a Src family kinase...
  5. doi Novel fluorescent dyes based on oligopropylamines for the in vivo staining of eukaryotic unicellular algae
    V V Annenkov
    Limnological Institute of Siberian Branch, Russian Academy of Sciences, 660033 Irkutsk, Russia
    Anal Biochem 407:44-51. 2010
    ..siliceous frustules of diatoms at concentrations at least 10 times lower than those required for staining with HCK-123. NBD-N3 also efficiently stained other subcellular vesicles of eukaryotic unicellular algae...
  6. pmc Two isoforms of murine hck, generated by utilization of alternative translational initiation codons, exhibit different patterns of subcellular localization
    P Lock
    Ludwig Institute for Cancer Research, Royal Melbourne Hospital, Parkville, Victoria, Australia
    Mol Cell Biol 11:4363-70. 1991
    ..Our results indicate that translation of murine p59hck initiates from a CTG codon located 21 codons 5' of an ATG that is utilized to generate p56hck...
  7. pmc Novel protein-tyrosine kinase gene (hck) preferentially expressed in cells of hematopoietic origin
    S F Ziegler
    Mol Cell Biol 7:2276-85. 1987
    ..Here we report the characterization of a novel human protein-tyrosine kinase gene (hck) that is primarily expressed in hematopoietic cells, particularly granulocytes...
  8. pmc Identification of a human gene (HCK) that encodes a protein-tyrosine kinase and is expressed in hemopoietic cells
    N Quintrell
    Mol Cell Biol 7:2267-75. 1987
    ..We have designated the gene as HCK (hemopoietic cell kinase) because its expression is prominent in the lymphoid and myeloid lineages of hemopoiesis...
  9. 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
    We have examined the differential binding of Hck and Fyn to HIV-1 Nef to elucidate the structural basis of SH3 binding affinity and specificity...
  10. pmc Myristoylation and differential palmitoylation of the HCK protein-tyrosine kinases govern their attachment to membranes and association with caveolae
    S M Robbins
    Department of Microbiology, University of California, San Francisco 94143 0552, USA
    Mol Cell Biol 15:3507-15. 1995
    ..HCK encodes two versions of a protein-tyrosine kinase, with molecular weights of 59,000 (p59hck) and 61,000 (p61hck). The two proteins arise from a single mRNA by alternative initiations of translation...
  11. pmc Proline-rich (PxxP) motifs in HIV-1 Nef bind to SH3 domains of a subset of Src kinases and are required for the enhanced growth of Nef+ viruses but not for down-regulation of CD4
    K Saksela
    Rockefeller University, New York, NY 10021
    EMBO J 14:484-91. 1995
    ..Nef PxxP motifs show specific binding to biotinylated SH3 domains of Hck and Lyn, but not to those of other tested Src family kinases or less related proteins...
  12. ncbi The solution structure of HIV-1 Nef reveals an unexpected fold and permits delineation of the binding surface for the SH3 domain of Hck tyrosine protein kinase
    S Grzesiek
    Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Struct Biol 3:340-5. 1996
    ..The binding surface of Nef for the SH3 domain of Hck tyrosine protein kinase has been mapped and reveals a non-contiguous (in terms of amino-acid sequence) interaction ..
  13. 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 crystal structure of the haematopoietic cell kinase Hck has been determined at 2.6/2.9 A resolution...
  14. ncbi Activation of the Src-family tyrosine kinase Hck by SH3 domain displacement
    I Moarefi
    Laboratories of Molecular Biophysics, Howard Hughes Medical Institute, The Rockefeller University, New York 10021, USA
    Nature 385:650-3. 1997
    The protein Hck is a member of the Src family of non-receptor tyrosine kinases which is preferentially expressed in haematopoietic cells of the myeloid and B-lymphoid lineages...
  15. ncbi SH3-mediated Hck tyrosine kinase activation and fibroblast transformation by the Nef protein of HIV-1
    S D Briggs
    Eppley Institute for Research in Cancer, University of Nebraska Medical Center, Omaha, Nebraska 68198 6805, USA
    J Biol Chem 272:17899-902. 1997
    ..virus-1 (HIV-1) has previously been shown to bind with high affinity and specificity in vitro to the SH3 domain of Hck, a Src family member expressed primarily in myeloid cells...
  16. ncbi RT loop flexibility enhances the specificity of Src family SH3 domains for HIV-1 Nef
    S Arold
    Centre de Biochimie Structurale, UMR C9955 CNRS, U414 INSERM, Universite Montpellier 1, France
    Biochemistry 37:14683-91. 1998
    ..a ligand recognize different SH3 domains? We present the crystal structure of the unbound SH3 domain from hemopoietic cell kinase (Hck) which is a member of the Src family of tyrosine kinases...
  17. ncbi The Src-like tyrosine kinase Hck is activated by granulocyte colony-stimulating factor (G-CSF) and docks to the activated G-CSF receptor
    A C Ward
    Institute of Hematology, Erasmus University Rotterdam, The
    Biochem Biophys Res Commun 251:117-23. 1998
    ..The hematopoietic cell kinase (Hck) is a member of the Src-family of kinases known to be expressed in cells of the granulocytic ..
  18. ncbi The proto-oncogene p120(Cbl) is a downstream substrate of the Hck protein-tyrosine kinase
    C J Howlett
    Department of Oncology, University of Calgary, Calgary, Alberta, Canada
    Biochem Biophys Res Commun 257:129-38. 1999
    b>Hematopoietic cell kinase (Hck) is a member of the Src-family of protein tyrosine kinases...
  19. pmc Simian immunodeficiency virus and human immunodeficiency virus type 1 nef proteins show distinct patterns and mechanisms of Src kinase activation
    A L Greenway
    AIDS Cellular Biology Unit, Macfarlane Burnet Center for Medical Research, Fairfield, Victoria 3078, Australia
    J Virol 73:6152-8. 1999
    ..show here that the Nef protein encoded by SIVmac239 interacts with and also activates the human Src kinases Lck and Hck. This is in direct contrast to the inhibitory effect of HIV type 1 (HIV-1) Nef on Lck catalytic activity...
  20. ncbi The conserved core of human immunodeficiency virus type 1 Nef is essential for association with Lck and for enhanced viral replication in T-lymphocytes
    H Cheng
    Department of Microbiology and Pediatrics, New York University School of Medicine, New York, New York 10016, USA
    Virology 264:5-15. 1999
    ..The Nef proteins from HIV-1 and SIV bind to Lck as well as Hck, Lyn, and Fyn...
  21. ncbi SH3 domains with high affinity and engineered ligand specificities targeted to HIV-1 Nef
    M Hiipakka
    Institute of Medical Technology, University of Tampere, Tampere, FIN 33101, Finland
    J Mol Biol 293:1097-106. 1999
    The avid binding of HIV-1 Nef to the Src homology-3 (SH3) domain of Hck (KD 250 nM) has been shown to involve an interaction between the RT-loop of Hck-SH3 and residues in Nef outside of its prototypic polyproline type II (PPII) helix-..
  22. ncbi Affinity of Src family kinase SH3 domains for HIV Nef in vitro does not predict kinase activation by Nef in vivo
    S D Briggs
    Eppley Institute for Research in Cancer and Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA
    Biochemistry 39:489-95. 2000
    ..Previous studies have shown that the SH3 domains of Hck and Lyn bind to Nef via proline-rich sequences in vitro, identifying these Src-related kinases as potential targets ..
  23. ncbi Lack of palmitoylation redirects p59Hck from the plasma membrane to p61Hck-positive lysosomes
    S Carreno
    Institut de Pharmacologie et de Biologie Structurale, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5089, 31077 Toulouse, France
    J Biol Chem 275:36223-9. 2000
    b>Hck, a protein-tyrosine kinase of phagocytes, is the unique member of the Src family expressed under two alternatively translated isoforms differing in their N-terminal site of acylation: p61(Hck) has an additional 21-amino acid sequence ..
  24. ncbi HIV-1 Nef promotes survival of myeloid cells by a Stat3-dependent pathway
    S D Briggs
    Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
    J Biol Chem 276:25605-11. 2001
    ..Nef binds with high affinity to the SH3 domain of the myeloid-restricted tyrosine kinase Hck in vitro, identifying this Src-related kinase as a possible cellular target for Nef in macrophages...
  25. ncbi Inhibition of cellular functions of HIV-1 Nef by artificial SH3 domains
    M Hiipakka
    Institute of Medical Technology, University of Tampere, Tampere, FIN 33014, Finland
    Virology 286:152-9. 2001
    ..Studies on binding of HIV-1 Nef to the SH3 domain of the Hck tyrosine kinase have indicated an important role for the SH3 RT-loop region in ligand binding...
  26. pmc The pathogenicity of human immunodeficiency virus (HIV) type 1 Nef in CD4C/HIV transgenic mice is abolished by mutation of its SH3-binding domain, and disease development is delayed in the absence of Hck
    Z Hanna
    Laboratory of Molecular Biology, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada
    J Virol 75:9378-92. 2001
    ..We also studied whether Hck, one of the effectors previously found to bind to this PXXP motif of Nef, was involved in disease development...
  27. ncbi SH3-dependent stimulation of Src-family kinase autophosphorylation without tail release from the SH2 domain in vivo
    Edwina C Lerner
    Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    Nat Struct Biol 9:365-9. 2002
    ..Here we show that SH3-dependent activation of the Src family member Hck by HIV-1 Nef binding or by SH2-kinase linker mutation does not affect tail tyrosine phosphorylation in fibroblasts...
  28. 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
    ..tyrosine phosphorylation and stimulation of DNA binding activity by five members of the Src kinase family (Src, Hck, Lyn, Fyn, and Fgr). We also observed stable STAT3.Src family kinase complex formation in this system...
  29. ncbi HIV-1 Nef control of cell signalling molecules: multiple strategies to promote virus replication
    Alison L Greenway
    Macfarlane Burnet Institute for Medical Research and Public Health, Cnr Commercial and Punt Roads, Melbourne, Victoria 3004, Australia
    J Biosci 28:323-35. 2003
    ....
  30. pmc Two distinct phosphorylation pathways have additive effects on Abl family kinase activation
    Keith Q Tanis
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA
    Mol Cell Biol 23:3884-96. 2003
    ..2- and 6.2-fold increases in kinase activity, respectively. We also find that the Src family kinase Hck phosphorylates the Abl and Arg activation loops, leading to an additional twofold stimulation of kinase activity...
  31. pmc CSF-induced and HIV-1-mediated distinct regulation of Hck and C/EBPbeta represent a heterogeneous susceptibility of monocyte-derived macrophages to M-tropic HIV-1 infection
    Iwao Komuro
    Department of Immunology, National Institute of Infectious Diseases, Toyama 1 23 1, Shinjuku ku, Tokyo 162 8640, Japan
    J Exp Med 198:443-53. 2003
    ..M-MPhi express a high level of Hck and a large isoform of C/EBPbeta, and HIV-1 infection increases the expression of Hck but not of C/EBPbeta...
  32. 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
    ..ACK1 interacts most strongly with the SH3 domains of Src family kinases (Src or Hck) via its C-terminal proline-rich domain...
  33. ncbi Physical and functional interaction between Hck tyrosine kinase and guanine nucleotide exchange factor C3G results in apoptosis, which is independent of C3G catalytic domain
    R Shivakrupa
    Centre for Cellular and Molecular Biology, Hyderabad 500 007, India
    J Biol Chem 278:52188-94. 2003
    The hematopoietic cell kinase Hck is a Src family tyrosine kinase expressed in cells of myelomonocytic lineage, B lymphocytes, and embryonic stem cells...
  34. ncbi Conserved residues in the HIV-1 Nef hydrophobic pocket are essential for recruitment and activation of the Hck tyrosine kinase
    Hyun Jung Choi
    Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, E1240 Biomedical Science Tower, Pittsburgh, PA 15261, USA
    J Mol Biol 343:1255-68. 2004
    ..Nef binds to the macrophage-specific Src family member Hck through its SH3 domain, resulting in constitutive kinase activation capable of transforming rodent fibroblasts...
  35. ncbi HIV-1 Nef interferes with M-CSF receptor signaling through Hck activation and inhibits M-CSF bioactivities
    Shinya Suzu
    Division of Hematopoiesis, Center for AIDS Research, Kumamoto University, Honjo 2 2 1, Kumamoto 860 0811, Japan
    Blood 105:3230-7. 2005
    HIV-1 Nef protein is a major determinant of the pathogenicity of the virus. It has been shown that Nef activates Hck, a member of Src family kinase, in monocytes/macrophages and that the interaction is critical for AIDS-like disease ..
  36. pmc Identification of preferred protein interactions by phage-display of the human Src homology-3 proteome
    Satu Kärkkäinen
    Institute of Medical Technology, University of Tampere and Tampere University Hospital, Biokatu 8, Tampere 33014, Finland
    EMBO Rep 7:186-91. 2006
    ....
  37. pmc HIV-1 Nef selectively activates Src family kinases Hck, Lyn, and c-Src through direct SH3 domain interaction
    Ronald P Trible
    Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    J Biol Chem 281:27029-38. 2006
    ..We expressed Fgr, Fyn, Hck, Lck, Lyn, and Yes as well as c-Src in yeast and found that each kinase was active and induced growth suppression...
  38. ncbi Interaction between Hck and HIV-1 Nef negatively regulates cell surface expression of M-CSF receptor
    Masateru Hiyoshi
    Division of Hematopoiesis, Center for AIDS Research, Kumamoto University, Honjo 2 2 1, Kumamoto City, Kumamoto 860 0811, Japan
    Blood 111:243-50. 2008
    Nef is a multifunctional pathogenetic protein of HIV-1, the interaction of which with Hck, a Src tyrosine kinase highly expressed in macrophages, has been shown to be responsible for the development of AIDS...
  39. ncbi HIV-1 Nef assembles a Src family kinase-ZAP-70/Syk-PI3K cascade to downregulate cell-surface MHC-I
    Chien Hui Hung
    Vollum Institute, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239, USA
    Cell Host Microbe 1:121-33. 2007
    ..The discovery of this Nef-SFK-ZAP-70/Syk-PI3K signaling pathway explains the hierarchal role of the Nef motifs in effecting immunoevasion...
  40. pmc Protein protein interaction inhibition (2P2I) combining high throughput and virtual screening: Application to the HIV-1 Nef protein
    Stephane Betzi
    Bioénergétique et Ingénierie des Protéines Laboratory, Centre National de la Recherche Scientifique Institut de Biologie Structurale et Microbiologie, 31 Chemin Joseph Aiguier, 13402 Marseille Cedex 20, France
    Proc Natl Acad Sci U S A 104:19256-61. 2007
    ....
  41. doi Dys-regulated activation of a Src tyroine kinase Hck at the Golgi disturbs N-glycosylation of a cytokine receptor Fms
    Ranya Hassan
    Division of Hematopoiesis, Center for AIDS Research, Kumamoto University, Kumamoto, Kumamoto, Japan
    J Cell Physiol 221:458-68. 2009
    HIV-1 Nef accelerates the progression to AIDS by binding with and activating a Src kinase Hck, but underlying molecular basis is not understood...
  42. pmc Chemical library screens targeting an HIV-1 accessory factor/host cell kinase complex identify novel antiretroviral compounds
    Lori Emert-Sedlak
    Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    ACS Chem Biol 4:939-47. 2009
    ..assay for inhibitors of Nef function by coupling it to one of its host cell binding partners, the Src-family kinase Hck. Hck activation is dependent upon Nef in this assay, providing a direct readout of Nef activity in vitro...
  43. doi HIV-1 Nef triggers macrophage fusion in a p61Hck- and protease-dependent manner
    Christel Verollet
    Département Mécanismes Moléculaires des Infections Mycobactériennes, Institut de Pharmacologie et de Biologie Structurale, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5089, France
    J Immunol 184:7030-9. 2010
    ..Nef has been shown to activate hematopoietic cell kinase (Hck), a Src tyrosine kinase specifically expressed in phagocytes, through a well-described polyproline-..
  44. pmc Small molecule inhibition of HIV-1-induced MHC-I down-regulation identifies a temporally regulated switch in Nef action
    Jimmy D Dikeakos
    Vollum Institute, Oregon Health and Science University, Portland, OR 97239, USA
    Mol Biol Cell 21:3279-92. 2010
    ..Together, these studies resolve the seemingly controversial models that describe Nef-induced MHC-I down-regulation and provide new insights into the mechanism of Nef action...
  45. pmc Structure, dynamics, and Hck interaction of full-length HIV-1 Nef
    Jinwon Jung
    Department of Structural Biology and Pittsburgh Center for HIV Protein Interactions, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15260, USA
    Proteins 79:1609-22. 2011
    ..of an NMR structural investigation on full-length Nef and its interaction with the entire regulatory domain of Hck (residues 72-256; Hck32L)...
  46. pmc Molecular design, functional characterization and structural basis of a protein inhibitor against the HIV-1 pathogenicity factor Nef
    Sebastian Breuer
    Abteilung Physikalische Biochemie, Max Planck Institut fur molekulare Physiologie, Dortmund, Germany
    PLoS ONE 6:e20033. 2011
    ..Structure determination of the Nef-inhibitor complex reveals the molecular basis for binding specificity. These results establish Nef-NI interfaces as promising leads for the development of potent Nef inhibitors...
  47. pmc HIV-1 Nef induces proinflammatory state in macrophages through its acidic cluster domain: involvement of TNF alpha receptor associated factor 2
    Giorgio Mangino
    Department of Biology, University Roma Tre, Rome, Italy
    PLoS ONE 6:e22982. 2011
    ....
  48. pmc The identification of a small molecule compound that reduces HIV-1 Nef-mediated viral infectivity enhancement
    Nopporn Chutiwitoonchai
    Center for AIDS Research, Kumamoto University, Kumamoto, Japan
    PLoS ONE 6:e27696. 2011
    ..Meanwhile, the overexpression of the SH3 domain of the tyrosine kinase Hck, which binds to a PxxP motif in Nef, also reduced viral infectivity...
  49. pmc Nef alleles from all major HIV-1 clades activate Src-family kinases and enhance HIV-1 replication in an inhibitor-sensitive manner
    Purushottam S Narute
    Department of Infectious Disease and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
    PLoS ONE 7:e32561. 2012
    ..Representative Nef proteins from the major HIV-1 subtypes A1, A2, B, C, F1, F2, G, H, J and K strongly activated Hck and Lyn as well as c-Src to a lesser extent, demonstrating for the first time that Src-family kinase activation is ..
  50. pmc Identification of a highly conserved valine-glycine-phenylalanine amino acid triplet required for HIV-1 Nef function
    Pieter J Meuwissen
    Department of Clinical Chemistry, Microbiology, and Immunology, Ghent University, Ghent, B 9000, Belgium
    Retrovirology 9:34. 2012
    ..In this study, we aimed to study the functional importance of this VGF region...
  51. pmc Effector kinase coupling enables high-throughput screens for direct HIV-1 Nef antagonists with antiretroviral activity
    Lori A Emert-Sedlak
    Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA
    Chem Biol 20:82-91. 2013
    ..Because Nef lacks intrinsic enzymatic activity, we developed an assay that couples Nef to the activation of Hck, a Src family member and Nef effector protein...
  52. ncbi Hck enhances the adherence of lipopolysaccharide-stimulated macrophages via Cbl and phosphatidylinositol 3-kinase
    G Scholz
    Molecular Biology Laboratory, Ludwig Institute for Cancer Research, P O Box 2008, Royal Melbourne Hospital, Victoria 3050, Australia
    J Biol Chem 275:14615-23. 2000
    ..Immunoprecipitation experiments revealed that Cbl associates with Hck in Bac1.2F5 cells, while expression of an activated form of Hck in Bac1...
  53. ncbi Oligomerization is required for HIV-1 Nef-induced activation of the Src family protein-tyrosine kinase, Hck
    Huihui Ye
    Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, E1240 Biomedical Science Tower, Pittsburgh, Pennsylvania 15261, USA
    Biochemistry 43:15775-84. 2004
    b>Hck is a member of the Src protein-tyrosine kinase family and is expressed strongly in macrophages, an important HIV target cell...
  54. ncbi Human protein-tyrosine kinase gene HCK: expression and structural analysis of the promoter region
    U Lichtenberg
    Department of Microbiology and Immunology, University of California, San Francisco 94143
    Oncogene 7:849-58. 1992
    The vertebrate gene HCK encodes a protein-tyrosine kinase that is closely related to the product of the proto-oncogene SRC...
  55. ncbi Interleukin-3 regulates the activity of the LYN protein-tyrosine kinase in myeloid-committed leukemic cell lines
    T Torigoe
    Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia
    Blood 80:617-24. 1992
    ..These cells expressed four of the eight known SRC-family proto-oncogenes: lyn, fyn, yes, and hck. When these factor-dependent leukemic cell lines were deprived of lymphokine to achieve cellular quiescence and ..
  56. ncbi Resting murine neutrophils express functional alpha 4 integrins that signal through Src family kinases
    S Pereira
    Department of Laboratory Medicine, University of California, San Francisco, CA 94143, USA
    J Immunol 166:4115-23. 2001
    ..Neutrophils derived from hck(-/-)fgr(-/-)lyn(-/-) triple-knockout or hck(-/-)fgr(-/-) double-knockout mice failed to undergo respiratory burst ..
  57. ncbi Platelet/polymorphonuclear leukocyte adhesion: a new role for SRC kinases in Mac-1 adhesive function triggered by P-selectin
    P Piccardoni
    Department of Vascular Medicine and Pharmacology, G Bizzozero Laboratory of Blood and Vascular Cell Interactions, Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy
    Blood 98:108-16. 2001
    ..Adhesion of PMNLs to activated platelets or to CHO-P cells stimulated activity of LYN and HCK. Monoclonal antibody blockade of P-selectin or beta2-integrins reduced the activation of both kinases...
  58. pmc The Src family kinases Hck and Fgr regulate neutrophil responses to N-formyl-methionyl-leucyl-phenylalanine
    Laura Fumagalli
    Department of Pathology, Section of General Pathology, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy
    J Immunol 178:3874-85. 2007
    ..Deficiency of the Src family kinases Hck and Fgr have previously been found to regulate fMLP-induced degranulation...
  59. ncbi Deficiency of the Hck and Src tyrosine kinases results in extreme levels of extramedullary hematopoiesis
    C A Lowell
    Department of Microbiology and Immunology, University of California, San Francisco, USA
    Blood 87:1780-92. 1996
    Expression of the Src-family kinases--Src, Hck, and Fgr--increases dramatically during myeloid cell development...
  60. pmc Phosphorylated guanine nucleotide exchange factor C3G, induced by pervanadate and Src family kinases localizes to the Golgi and subcortical actin cytoskeleton
    Vegesna Radha
    Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007 India
    BMC Cell Biol 5:31. 2004
    ..C3G is activated upon phosphorylation at tyrosine 504 and therefore, determining the localization of phosphorylated C3G would provide an insight into its site of action in the cellular context...
  61. ncbi Bull testicular haploid germ cells express a messenger encoding for a truncated form of the protein tyrosine kinase HCK
    Claudia Lalancette
    Département d obstétrique gynécologie, Centre de Recherche en Biologie de la Reproduction, Université Laval and Endocrinologie de la Reproduction, Centre de recherche du CHUQ, Quebec, Canada
    Mol Reprod Dev 73:520-30. 2006
    ..homologous region specific to the family of src tyrosine kinases, and RNAs coding for c-src, c-yes, lyn, lck, and hck were identified in bull testis and haploid germ cells by RT-PCR...
  62. pmc Lipopolysaccharide (LPS)-induced macrophage activation and signal transduction in the absence of Src-family kinases Hck, Fgr, and Lyn
    F Meng
    Department of Laboratory Medicine, University of California, San Francisco 94143 0724, USA
    J Exp Med 185:1661-70. 1997
    ..Recently, an increasing amount of evidence suggests that protein tyrosine kinases especially the Src-family kinases Hck, Fgr, and Lyn, play important roles in LPS signaling...
  63. pmc Myeloid Src kinases regulate phagocytosis and oxidative burst in pneumococcal meningitis by activating NADPH oxidase
    Robert Paul
    Department of Neurology, Klinikum Grosshadern, Ludwig Maximilians University, Marchioninistr 15, D 81377 Munich, Germany
    J Leukoc Biol 84:1141-50. 2008
    ..Myeloid Src family kinases (SFKs) p59/61(hck) (Hck), p58(c-fgr) (Fgr), and p53/56(lyn) (Lyn) are known to control integrin beta(2) signal transduction and ..
  64. pmc The absence of Hck, Fgr, and Lyn tyrosine kinases augments lung innate immune responses to Pneumocystis murina
    Michael P Nelson
    Department of Medicine, University of Alabama Birmingham, 1900 University Blvd, THT 437A, Birmingham, AL 35294, USA
    Infect Immun 77:1790-7. 2009
    ..As myeloid cells preferentially express the SFKs Hck, Fgr, and Lyn, we questioned the role of these kinases in innate immune responses to Pneumocystis murina...
  65. ncbi CD45 regulates Src family member kinase activity associated with macrophage integrin-mediated adhesion
    T Roach
    Division of Infectious Diseases, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Curr Biol 7:408-17. 1997
    ..Here, we show that CD45 is also important in downregulating the kinase activity of Src family members during integrin-mediated adhesion in macrophages...
  66. ncbi Identification and activation of Src family kinases in primary megakaryocytes
    Brian J Lannutti
    Puget Sound Blood Center, 921 Terry Avenue, Seattle, WA 98104 1256, USA
    Exp Hematol 31:1268-74. 2003
    ..In this study, we examine which of the eight Src family members are expressed in primary megakaryocytes (MKs) and determine which of these become activated in response to TPO...
  67. pmc Src family kinases mediate neutrophil adhesion to adherent platelets
    Virgilio Evangelista
    Laboratory of Vascular Biology and Pharmacology, Consorzio Mario Negri Sud, Via Nazionale 8 A, 66030 Santa Maria Imbaro, Italy
    Blood 109:2461-9. 2007
    ..PMNs from alphaMbeta2(-/-), hck(-/-)fgr(-/-), and hck(-/-)fgr(-/-)lyn(-/-) mice had an impaired capacity to adhere with activated platelets in ..
  68. ncbi Lyn, one of the Src-family tyrosine kinases expressed in phagocytes, plays an important role in beta2 integrin-signalling pathways in opsonized zymosan-activated macrophage-like U937 cells
    Reiko Adachi
    Division of Biosignaling, National Institute of Health Sciences, Setagaya Ku, Tokyo, Japan
    Cell Biochem Funct 25:323-33. 2007
    We have investigated the contribution of Hck, Lyn and Fgr, highly expressed Src family tyrosine kinases (SFKs) in signalling pathways in opsonized zymosan (OZ)-activated phagocytes by using short interfering RNAs (siRNAs)...
  69. ncbi Adhesion-dependent degranulation of neutrophils requires the Src family kinases Fgr and Hck
    A Mocsai
    Institute of General Pathology, University of Verona, Italy
    J Immunol 162:1120-6. 1999
    ..Double knockout hck-/- fgr-/- PMN adherent to collagen or fibrinogen failed to release lactoferrin in response to TNF-alpha but ..
  70. ncbi The Src family kinases Hck and Fgr are dispensable for inside-out, chemoattractant-induced signaling regulating beta 2 integrin affinity and valency in neutrophils, but are required for beta 2 integrin-mediated outside-in signaling involved in sustained a
    Cinzia Giagulli
    Department of Pathology, Section of General Pathology, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy
    J Immunol 177:604-11. 2006
    ..Addressing inside-out and outside-in signaling in hck(-/-)fgr(-/-) neutrophils, we found that Hck and Fgr do not regulate chemoattractant-induced activation of beta(2) ..
  71. pmc A beta 1 integrin signaling pathway involving Src-family kinases, Cbl and PI-3 kinase is required for macrophage spreading and migration
    F Meng
    Department of Laboratory Medicine, University of California at San Francisco 94143 0100, USA
    EMBO J 17:4391-403. 1998
    ..In hck-/-fgr-/-lyn-/- triple mutant cells, which are defective in spreading on fibronectin-coated surfaces in vitro and ..
  72. ncbi The regulation of the expression of inducible nitric oxide synthase by Src-family tyrosine kinases mediated through MyD88-independent signaling pathways of Toll-like receptor 4
    Joo Y Lee
    Department of Nutrition, University of California Davis, ARS, Western Human Nutrition Research Center, Meyer Hall, 95616, USA
    Biochem Pharmacol 70:1231-40. 2005
    ..nitric oxide synthase (iNOS) induced by LPS were not affected in macrophages deficient in three STKs (Lyn, Hck, and Fgr)...
  73. ncbi Src family kinases phosphorylate the Bcr-Abl SH3-SH2 region and modulate Bcr-Abl transforming activity
    Malcolm A Meyn
    Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    J Biol Chem 281:30907-16. 2006
    ..Recently, we observed that inhibition of myeloid Src family kinase activity (e.g. Hck, Lyn, and Fyn) induces growth arrest and apoptosis in Bcr-Abl-transformed cells, suggesting that cell ..
  74. ncbi Inhibition of IL-6-dependent growth of myeloma cells by an acidic peptide repressing the gp130-mediated activation of Src family kinases
    A Hausherr
    Clinical Cooperation Group Gene Therapy, GSF National Research Center for Environment and Health, Munich, Germany
    Oncogene 26:4987-98. 2007
    An acidic domain (AD) of gp130 was previously found to interact with the Src family kinase (SFK) Hck. Here, the influence of myristoylated peptides derived from this AD was assessed in the mouse myeloma cell line, 7TD1...
  75. ncbi Lck associates with and is activated by Kit in a small cell lung cancer cell line: inhibition of SCF-mediated growth by the Src family kinase inhibitor PP1
    G W Krystal
    Department of Medicine, Medical College of Virginia Commonwealth University, McGuire Veterans Affairs Medical Center, Richmond 23249, USA
    Cancer Res 58:4660-6. 1998
    ..Low levels of Src, Hck, and Yes were also expressed in the H526 cell line; only Yes showed a consistent increase in specific activity, ..
  76. ncbi The Src family kinases Hck and Fgr negatively regulate neutrophil and dendritic cell chemokine signaling via PIR-B
    Hong Zhang
    Department of Laboratory Medicine, University of California, San Francisco, San Francisco, California 94143, USA
    Immunity 22:235-46. 2005
    ..However, neutrophils derived from hck-/-fgr-/- mice and dendritic cells (DCs) from fgr-/- animals manifested significantly higher intracellular signaling ..
  77. ncbi Dasatinib (BMS-354825) inhibits Stat5 signaling associated with apoptosis in chronic myelogenous leukemia cells
    Sangkil Nam
    Molecular Medicine, Beckman Research Institute, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA 91010, USA
    Mol Cancer Ther 6:1400-5. 2007
    ..In this study, we confirm that dasatinib inhibits tyrosine phosphorylation of SFKs, including Src, Hck, and Lyn, in K562 human CML cells...
  78. ncbi Gene expression analysis illuminates the transcriptional programs underlying the functional activity of ex vivo-expanded granulocytes
    Li Ting Huang
    Department of Chemical and Biological Engineering, Northwestern University, Evanston, Illinois, USA
    Physiol Genomics 31:114-25. 2007
    ..was similar for most Fc gamma receptor-mediated phagocytosis signaling proteins, including high-level expression of Hck, Fgr, and the actin-related protein 2/3 complex...
  79. pmc Mapping the conformational transition in Src activation by cumulating the information from multiple molecular dynamics trajectories
    Sichun Yang
    Department of Biochemistry and Molecular Biology, University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA
    Proc Natl Acad Sci U S A 106:3776-81. 2009
    ..conformational transition pathway is presented to bridge the inactive and active states of the catalytic domain of Hck. The information from a large number (78) of independent all-atom molecular dynamics trajectories with explicit ..
  80. pmc c-Abl and Src-family kinases cross-talk in regulation of myeloid cell migration
    Anna Baruzzi
    Department of Pathology, University of Verona, Verona, Italy
    FEBS Lett 584:15-21. 2010
    Cytoskeleton dynamics are regulated by Src-family tyrosine kinases (SFKs) and c-Abl. We found that the SFK members Hck and c-Fgr regulate tyrosine phosphorylation of c-Abl and c-Abl associates with beta1 integrin-bound Hck or c-Fgr in ..
  81. ncbi The carboxy-terminal region of the granulocyte colony-stimulating factor receptor transduces a phagocytic signal
    Valeria Santini
    Department of Hematology, University of Florence, Florence, Italy
    Blood 101:4615-22. 2003
    ..We also demonstrated that tyrosine phosphorylation of the Src kinases Hck and Lyn occurs following G-CSF stimulation of cells expressing WT G-CSF-R, but that Hck is not phosphorylated in ..
  82. ncbi Immunohistochemical profile of common epithelial neoplasms arising in the kidney
    Mi Kyung Kim
    Department of Diagnostic Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
    Appl Immunohistochem Mol Morphol 10:332-8. 2002
    ..for CD10, vimentin (VIM), E-cadherin (E-CD), cytokeratins (CK) 7, 8, 19, and 20, high molecular weight keratin (HCK), and peanut lectin agglutinin (PL) (Arachis hypogaea) were performed on 45 (96 for CK7, CK20) conventional (CC), ..
  83. doi Reduced expression of SRC family kinases decreases PI3K activity in NBS1-/- lymphoblasts
    Daniel Sagan
    Institute of Radiation Biology, Helmholtz Centre Munich, Neuherberg, Germany
    Biochem Biophys Res Commun 377:181-6. 2008
    ..Especially, only minor amounts of the kinases LCK and HCK are expressed in the NBS1(-/-) cell lines as compared to the consanguineous NBS1(+/-) cells...
  84. pmc E-selectin engages PSGL-1 and CD44 through a common signaling pathway to induce integrin alphaLbeta2-mediated slow leukocyte rolling
    Tadayuki Yago
    Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA
    Blood 116:485-94. 2010
    ..of PSGL-1 or CD44 triggered slow rolling through a common, lipid raft-dependent pathway that used the SFKs Hck and Lyn as well as Fgr...
  85. pmc Herpesvirus ateles gene product Tio interacts with nonreceptor protein tyrosine kinases
    J C Albrecht
    Institut fur Klinische und Molekulare Virologie, Universitat Erlangen Nurnberg, 91054 Erlangen, Germany
    J Virol 73:4631-9. 1999
    ..Binding analyses indicated a direct interaction of Tio with the SH3 domains of Lyn, Hck, Lck, Src, Fyn, and Yes. In addition, tyrosine-phosphorylated Tio bound to the SH2 domains of Lck, Src, or Fyn...
  86. pmc Myeloproliferative disease induced by TEL-PDGFRB displays dynamic range sensitivity to Stat5 gene dosage
    Jennifer A Cain
    Department of Internal Medicine, Division of Oncology, Washington University Siteman Cancer Center, 550 S Euclid Avenue, St Louis, MO 63110, USA
    Blood 109:3906-14. 2007
    ..In contrast, Src family kinases Lyn, Hck, and Fgr and the Stat family member Stat1 were dispensable for TEL-PDGFRB disease...
  87. pmc Hematopoietic cell kinase associates with the 40S ribosomal subunit and mediates the ribotoxic stress response to deoxynivalenol in mononuclear phagocytes
    Heekyong Bae
    Center for Integrative Toxicology, Michigan State University, East Lansing, Michigan 48824 1224, USA
    Toxicol Sci 115:444-52. 2010
    ..macrophage-a response that is dependent on both double-stranded RNA-activated protein kinase (PKR) and hematopoietic cell kinase (Hck)...
  88. ncbi Proto-oncogene expression in bovine peripheral blood leukemic lymphocytes during their spontaneous proliferation, differentiation and apoptosis in vitro
    A V Kalvelyte
    Institute of Biochemistry, Vilnius, Lithuania
    Leuk Res 22:135-43. 1998
    ..Transcripts of c-fos, c-myc, c-myb, A-raf, c-raf1, hck, IL-2 receptor alpha-chain (IL-2R alpha) were found in lymphocytes at the peak of their proliferative activity in ..
  89. ncbi Tyrosine protein kinases and spermatogenesis: truncation matters
    Abraham L Kierszenbaum
    Department of Cell Biology and Anatomical Sciences, The Sophie Davis School of Biomedical Education The City University of New York Medical School, New York, NY 10031, USA
    Mol Reprod Dev 73:399-403. 2006
    ..Examples include the truncated forms of Src tyrosine kinase hematopoietic cell kinase (Hck), FerT, and tr-kit...
  90. ncbi Effect of mixed crowding on refolding of human muscle creatine kinase
    Zhi Min Lin
    Department of Biochemistry and Molecular Biology, Beijing Normal University, Beijing Key Laboratory, Beijing 100875, P R China
    Protein Pept Lett 17:1426-35. 2010
    ..mixed crowding agents containing both sucrose and dextran 70 on refolding process of human muscle creatine kinase (HCK) were studied by enzyme activity assay and aggregation measurements...
  91. ncbi Reconstitution of the B cell antigen receptor signaling components in COS cells
    S J Saouaf
    Department of Oncology, Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543, USA
    J Biol Chem 270:27072-8. 1995
    ..Of the tyrosine kinases transfected (Lyn, Blk, Hck, Syk, Fyn), only Blk was able to phosphorylate and subsequently associate with cotransfected Ig alpha and Ig beta ..
  92. ncbi Rab5a GTPase regulates fusion between pathogen-containing phagosomes and cytoplasmic organelles in human neutrophils
    Nasrin Perskvist
    Department of Medical Microbiology, Faculty of Health Science, Linkoping University, SE 581 85 Linkoping, Sweden
    J Cell Sci 115:1321-30. 2002
    ..that lactoferrin (a constituent of secondary granules) and LAMP-1 were incorporated into both SCP and MCP, whereas hck (marker of azurophil granules) interacted solely with SCP...
  93. ncbi Anatomy of a structural pathway for activation of the catalytic domain of Src kinase Hck
    Nilesh K Banavali
    Department of Physiology and Biophysics, Weill Medical College of Cornell University, New York, New York 10021, USA
    Proteins 67:1096-112. 2007
    ..Crystallographic studies indicate that activation of Hematopoietic cell kinase (Hck), a member of the Src kinase family, is accompanied structurally by a large conformational change ..
  94. pmc Lysophosphatidylcholines activate G2A inducing G(αi)₋₁-/G(αq/)₁₁- Ca²(+) flux, G(βγ)-Hck activation and clathrin/β-arrestin-1/GRK6 recruitment in PMNs
    Samina Y Khan
    Bonfils Blood Center, Denver, CO 80230, USA
    Biochem J 432:35-45. 2010
    ..also caused the release of the G(βγ) subunit which demonstrated a physical interaction (FRET+) with activated Hck (haemopoietic cell kinase; Tyr⁴¹¹)...
  95. ncbi Fgr deficiency results in defective eosinophil recruitment to the lung during allergic airway inflammation
    Lucia Vicentini
    Department of Pathology, Section of General Pathology, University of Verona, Italy
    J Immunol 168:6446-54. 2002
    ..tissue and airway eosinophilia were markedly reduced in fgr(-/-) mice, whereas mice with the sole deficiency of Hck, another Src family member, responded normally...
  96. doi Gene expression profiling of alpha-radiation-induced rat osteosarcomas: identification of dysregulated genes involved in radiation-induced tumorigenesis of bone
    Kazuhiro Daino
    Laboratoire de Cancerologie Experimentale, IRCM, DSV, CEA, Fontenay aux Roses, France
    Int J Cancer 125:612-20. 2009
    ..g., Nme3, Blcap and Rrm1), Src tyrosine kinase signaling (e.g., Hck, Shf, Arhgap29, Cttn and Akap12), and Wnt/beta-catenin signaling (e.g., Fzd6, Lzic, Dkk3 and Ctnna1) pathways...
  97. ncbi RA70 is a src kinase-associated protein expressed ubiquitously
    Y Kouroku
    Division of Development and Differentiation, National Institute of Neuroscience, NCNP, Kodaira, Tokyo, 187 8502, Japan
    Biochem Biophys Res Commun 252:738-42. 1998
    ..Interaction between RA70 and src family kinases, Fyn, Hck and Lyn, was detected during monocytes/macrophage-differentiation of U937 cells...
  98. ncbi Intramolecular binding of a proximal PPII helix to an SH3 domain in the fusion protein SH3Hck : PPIIhGAP
    W H Gmeiner
    Department of Biochemistry, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA
    Cell Biochem Biophys 35:115-26. 2001
    SH3 domains are a conserved feature of many nonreceptor protein tyrosine kinases, such as Hck, and often function in substrate recruitment and regulation of kinase activity...
  99. ncbi Constitutive exclusion of Csk from Hck-positive membrane microdomains permits Src kinase-dependent proliferation of Theileria-transformed B lymphocytes
    Martin Baumgartner
    Laboratoire de Signalisation Immunoparasitaire, Departement d Immunologie, Institut Pasteur, Paris, France
    Blood 101:1874-81. 2003
    ..expression; correspondingly, the amount of Csk associated with PAG/Cbp in GEMs increased markedly, whereas PTK Hck accumulation in GEM fractions did not alter on growth arrest...
  100. ncbi Src-CrkII-C3G-dependent activation of Rap1 switches growth hormone-stimulated p44/42 MAP kinase and JNK/SAPK activities
    Ling Ling
    Institute of Molecular and Cell Biology, 30 Medical Drive, Singapore 117609
    J Biol Chem 278:27301-11. 2003
    ..In addition, we demonstrated that C3G-Rap1 mediated CrkII enhancement of GH-stimulated JNK/SAPK activity. We have therefore identified a linear JAK2-independent pathway switching GH-stimulated p44/42 MAP kinase and JNK/SAPK activities...
  101. ncbi Evidence that activation of Src family kinase is not required for fertilization-associated [Ca2+]i oscillations in mouse eggs
    Manabu Kurokawa
    Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003, USA
    Reproduction 127:441-54. 2004
    ..We detected a Hck-like protein and tyrosine-phosphorylated proteins in soluble and insoluble sperm fractions, respectively...

Research Grants53

  1. Src Family Tyrosine Kinases in Tumor Cell Signaling
    THOMAS SMITHGALL; Fiscal Year: 2007
    ..Using fibroblast and myeloid cell transformation assays, we will test this idea by co-expressing Hck and Lyn with regions of Bcr-Abl previously shown to bind to these myeloid Src family members in vitro...
  2. Src Family Kinases as Molecular Targets for HIV/Nef
    THOMAS EDWARD SMITHGALL; Fiscal Year: 2010
    ..Work completed during the previous grant period shows that Nef binds and activates Hck, Lyn, and c-Src, all of which are expressed in HIV target cells...
  3. Dianne Cox; Fiscal Year: 2014
    ..a key factor in podosome turnover and chemotaxis and preliminary data suggest that the Src family tyrosine kinase Hck mediates WASP phosphorylation, which is required for MD diapedesis across an endothelium...
  4. Complexes of HIV-1 Nef with Src-family Kinases as Therapeutic Targets
    Lori A Emert Sedlak; Fiscal Year: 2010
    ..Nef binds and activates members of the Src protein-tyrosine kinase family, namely Hck, Lyn, and c-Src...
  5. Structural Biology of HIV Nef-Src Family Kinase Complexes
    THOMAS EDWARD SMITHGALL; Fiscal Year: 2010
    ..Nef interacts with multiple host cell signaling proteins, including the Src family kinases (SFKs) Hck, Lyn, and c-Src...
  6. Joanne I Yeh; Fiscal Year: 2016
    ..Nef works via host cell signaling proteins including Hck and other Src-family kinases (SFKs), suggesting that Nef-SFK complexes are present in all HIV-infected cell types...
  7. THOMAS EDWARD SMITHGALL; Fiscal Year: 2016
    ..activity, and functions by interacting with multiple host cell signaling proteins, including the Src-family kinases Hck, Lyn, and c-Src...
  8. SRC-LIKE KINASES IN INTERLEUKIN-3 RECEPTOR SIGNALING
    Steven Anderson; Fiscal Year: 2001
    ..fusion protein containing a 236 amino acid region of the cytoplasmic tail of the beta subunit to which both Hck and Fyn bind, will be used to identify both phosphotyrosine-dependent and independent binding sites for the ..
  9. Arrestin activation probed with mass spectrometry
    Eric Prossnitz; Fiscal Year: 2007
    ..Arrestins also associate with the Src-family kinases Src and Hck to initiate G protein-independent signaling pathways...
  10. Grant McFadden; Fiscal Year: 2014
    ..to 46 different human signaling phosphoproteins, and observed that MV infection specifically induces Stat5 and Hck activation in KG1 cells...
  11. CD-18 DEPENDENT/INDEPENDENT WBC RESPONSES IN THE LUNG
    CLAIRE DOERSCHUK; Fiscal Year: 2007
    ..In contrast, mice deficient in the leukocyte non-receptor Src tyrosine kinases Lyn, Fgr, and Hck, in the small GTPase Rac2, or in interferon-(IFN-g) have defects in S...
  12. Regulation of Alveolar Macrophage Phagocytosis
    Bruce Trapnell; Fiscal Year: 2006
    ..1 is required in AMs constitutively to stimulate their terminal differentiation and for expression of Fc?R?, Hck and possibly other downstream targets critical for effective Fc?R?-mediated phagocytosis...
  13. Mechanisms of Trichothecene Toxicity
    James Pestka; Fiscal Year: 2005
    ..Our central hypothesis is that double stranded RNA-activated protein kinase (PKR) and hematopoietic cell kinase (Hck) are critical for trichothecene-induced p38 activation and downstream toxicity...
  14. Acquiring robotic support for mass spectrometry core
    CRAIG MALBON; Fiscal Year: 2003
    ..this instrumentation in his proteomic analysis of tyrosine kinases, focusing upon the SH3-dependent partners of Hck and interacting protein partners for Jak2...
  15. Src Kinases in Ph+ Lymphoblastic Leukemia
    Shaoguang Li; Fiscal Year: 2009
    ..In support of this hypothesis, we identified three Src family kinases (Lyn, Hck, and Fgr) as key signaling molecules in the development of BCR-ABL-induced B-ALL but not CML (Nature Genetics 36,..
  16. p56lck Inhibitors as Potential Immunosuppressive Drugs.
    ALEXANDER MACKERELL; Fiscal Year: 2004
    ..Simultaneous use of the p56lck, Hck, Fyn, Src, Shc and ZAP-70 SH2 domains will allow for selectivity to be included in the computer screening process...
  17. Signaling by Cytoplasmic Tyrosine Kinases in Leukocytes
    Clifford Lowell; Fiscal Year: 2005
    ..studied the Src-family of tyrosine kinases using a panel of knockout mice that lack one or all Src-family members (Hck, Fgr, and Lyn) normally expressed in myeloid cells...
  18. RETROVIRUSES AND CANCER GENES
    J Bishop; Fiscal Year: 2000
    ..Most attention will be given to the protein-tyrosine kinases encoded by the proto-oncogenes SRC and HCK, and the transcription factors encoded by MYB and MYC...
  19. MULTIPURPOSE ARTHRITIS AND MUSCULOSKELETAL DISEASES CENT
    Richard Pope; Fiscal Year: 2001
    ..for novel B cell hyperactivity genes, define the mechanism of association between the protein tyrosine kinases hck and lyn with high affinity IgG receptor (FcgammaRI), and examine superantigen interactions with MHC II molecules to ..
  20. STRUCTURE ELUCIDATION OF PROTEINS BY MASS SPECTROMETRY
    David Smith; Fiscal Year: 2003
    ..This project will focus on hematopoietic cell kinase (Hck), which is strongly activated in vivo by the HIV Nef protein.
  21. Structural Biology of Tyrosine Kinase Regulation
    David Horita; Fiscal Year: 2004
    ..Inhibition of Hck prevents onset of diabetes in animal models, suggesting this protein as a target for anti- DM1 drug development...
  22. LPS-INDUCED SIGNALING IN MACROPHAGES
    Anthony DeFranco; Fiscal Year: 1999
    ..Experiments of AIM 2 will study the roles of the intracellular tyrosine kinases Syk, Hck, Lyn, and Fgr in initiating LPS signaling events by examining macrophages from mice made genetically defective in ..
  23. CHARACTERIZATION OF A SRC-RELATED GENE IN MACROPHAGES
    RICHARD MAKI; Fiscal Year: 1990
    The focus of this proposal is the tyrosine kinase, hck (hematopoietic cell kinase) expressed primarily in cells of the myloid lineage...
  24. COSTIMULATION AND T CELL ACTIVATION
    Andrey Shaw; Fiscal Year: 2003
    ..The recently solved crystal structures of the Src- kinases, lck and hck, suggest that an important mechanism for src-kinase activation will be via SH3 engagement...
  25. SIGNAL TRANSDUCTION PROBED BY CONSOLIDATED LIGANDS
    David Cowburn; Fiscal Year: 2000
    ..The proteins involved, Grb2, Lck, Hck, Crk, Abl, and STAT1 are central to growth factor mediated cell transformation, the immune response, causation of ..
  26. THE JUVENILE DIABETIC HEART
    RALPH SCOTT; Fiscal Year: 1980
    ..approximately 125 living juvenile diabetics who have been personally followed by one of the co-investigators (HCK) for periods up to 25 years...
  27. Targeting HIV-1 Nef with Small Molecules
    THOMAS SMITHGALL; Fiscal Year: 2008
    ..Previous work from our laboratory has shown that Nef binds and activates Hck, a Src family kinase (SFK) selectively expressed in macrophages, which are an essential HIV target cell and viral ..
  28. ENDOTOXIN AND SUSCEPTIBILITY TO TRICHOTHECENE MYCOTOXINS
    James Pestka; Fiscal Year: 2002
    ..Over the long term, this research will provide insight into adverse immunologic consequences that may occur in LPS-exposed individuals who are exposed to environmental toxicants." ..
  29. DIETARY LIPIDS AND EXPERIMENTAL IGA NEPHROPATHY
    James Pestka; Fiscal Year: 2009
    ..abstract_text> ..
  30. Selective Inhibitors of SRC Family Kinases in Neoplasia
    THOMAS SMITHGALL; Fiscal Year: 2002
    ..Combined with the in vitro assays, we hope to identify novel inhibitory activities that target specific Src kinase isoforms and oncogenic signaling pathways. ..
  31. Cytoplasmic Tyrosine Kinase Pathways and ES Cell Fate
    THOMAS EDWARD SMITHGALL; Fiscal Year: 2010
    ..The ultimate utility of stem cells in clinical medicine depends upon safe and effective methods for manipulating their renewal and differentiation in culture. ..
  32. REGULATION OF P93 C FES TYROSINE KINASE ACTIVITY
    THOMAS SMITHGALL; Fiscal Year: 2005
    ..These studies will help to elucidate the molecular mechanisms that regulate Fes tyrosine kinase activity and to identify the signal transduction pathways utilized by Fes to transmit signals for differentiation. ..
  33. Pittsburgh Molecular Libraries Screening Center(RMI)
    JOHN LAZO; Fiscal Year: 2008
    ..unreadable] [unreadable]..
  34. The biology of gastrin-ferric ion complexes
    GRAHAM BALDWIN; Fiscal Year: 2009
    ..Recognition that metal ions are essential for the biological activity of NAGs may permit the development of novel therapies for colon cancer. ..
  35. Bleomycin Hydrolase and Alzheimer's Disease
    JOHN LAZO; Fiscal Year: 2004
    ..These studies should provide new mechanistic information concerning the pathogenesis of AD as well as reagents for future therapeutic studies. ..
  36. Thrombopoietin Signaling: The Role of Src Kinases
    BRIAN LANNUTTI; Fiscal Year: 2007
    ..Understanding the signaling mechanisms of Mp1 and its interactions with other signaling molecules may lead to novel approaches in the treatment of a number of hematologic and other diseases. ..
  37. Mycobacteria Invasion and Persistence
    Eric Brown; Fiscal Year: 2007
    ..Determine how the GDP-mannose synthesis operon regulates macrophage activation and intracellular survival 3. Carry out a genetic screen for Mm genes specifically required for intracellular growth in macrophages. ..
  38. Chemical Complementation Assay for MKP-1 (RMI)
    JOHN LAZO; Fiscal Year: 2005
    ..This proposal will provide sufficient reagents, including cells and DMA transfection vectors, to permit the high throughput screening of 100,000 compounds. ..
  39. CD47 Homologues in Pathogenesis of Poxvirus Infection
    Eric Brown; Fiscal Year: 2003
    ..abstract_text> ..
  40. Molecular Epidemiology of Endometrial Cancer
    Chu Chen; Fiscal Year: 2007
    ..Efforts will also be devoted to generating risk indices through statistical modeling that integrate potential effects of genetic variants in the estrogen metabolism pathway and/or DNA repair pathways. ..
  41. MICROTUBULE/KERATIN INTERACTIONS DURING SPERMATOGENESIS
    ABRAHAM KIERSZENBAUM; Fiscal Year: 2002
    ..Engineering mouse models in which the expression of K9 is null, is important for both reproductive biology and cancer research. ..
  42. In Vitro High Throughput Screening Assay for MKP-1(RMI)
    JOHN LAZO; Fiscal Year: 2005
    ..No potent or selective small molecule inhibitors of this protein phosphatase are known. This proposal will provide sufficient reagents to permit a high throughput screening of 100,000 compounds. ..
  43. In Vitro High Throughput Screening Assay for MKP-3(RMI)
    JOHN LAZO; Fiscal Year: 2005
    ..Nonetheless, no potent or selective small molecule inhibitors of this protein phosphatase have been identified. This proposal will provide sufficient reagents to permit a high throughput screening of 100,000 compounds ..
  44. BIOCHEMICAL REGULATORS OF BLEOMYCIN INDUCED TUMORS
    JOHN LAZO; Fiscal Year: 2001
    ..The Specific Aims are to: 1) develop cells and mice deficient in BH, 2) develop cells and mice that overexpress BH, 3) isolate and characterize potential proteins that interact with BH and, 4) analyze the regulation of BH expression. ..
  45. Chemical Complementation Assay for MKP-3 (RMI)
    JOHN LAZO; Fiscal Year: 2005
    ..This proposal will provide sufficient reagents, including cells and DMA transfection vectors, to permit the high throughput screening of 100,000 compounds. ..
  46. ORAL CANCER: MOLECULAR PROFILES & CLINICAL OUTCOMES
    Chu Chen; Fiscal Year: 2010
    ..HPV plays an important etiologic role in some oropharyngeal cancers, we plan to determine and incorporate HPV genotypes in the analyses and interpretation of the study findings. ..
  47. CYCLIC AMP/ADENOSINE PATHWAY
    Edwin Jackson; Fiscal Year: 2002
    ..abstract_text> ..
  48. MOLECULAR EPIDEMIOLOGY OF LUNG CANCER
    Chu Chen; Fiscal Year: 2010
    ..g. Rosaceae fruits and Cruciferae vegetables), and food-derived nutrients (e.g. carotenoids, vitamin C, and vitamin E). ..
  49. INTERLEUKIN 6 AND HUMAN BILIARY EPITHELIAL PROLIFERATION
    Anthony Demetris; Fiscal Year: 2006
    ..abstract_text> ..
  50. BREAST CANCER AND GENE POLYMORPHISMS IN CHINESE WOMEN
    Chu Chen; Fiscal Year: 2003
    ..Our ultimate goal is to provide information to identify women at high risk of breast cancer, and to aid in the formulation of prevention strategies for these women. ..
  51. 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. ..