Activation of the PAK-related kinase by human immunodeficiency virus type 1 Nef in primary human peripheral blood lymphocytes and macrophages leads to phosphorylation of a PIX-p95 complex
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作者:
Brown, A
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机构:Rockefeller Univ, Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA
Brown, A
Wang, X
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机构:Rockefeller Univ, Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA
Wang, X
Sawai, E
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机构:Rockefeller Univ, Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA
Sawai, E
Cheng-Mayer, C
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机构:Rockefeller Univ, Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA
Cheng-Mayer, C
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[1] Rockefeller Univ, Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA
Human immunodeficiency virus type 1 (HIV-1) Nef enhances virus replication in both primary T lymphocytes and monocyte derived macrophages. This enhancement phenotype has been linked to the ability of Nef to modulate the activity of cellular kinases. We find that despite the reported high-affinity interaction between Nef and the Src kinase Hck in vitro, a Nef-Hck interaction in the context of HN-l-infected primary macrophages is not detectable. However, Nef binding and activation of the PAK-related kinase and phosphorylation of its substrate could be readily detected in both infected primary T lymphocytes and macrophages. Furthermore, we show that this substrate is a complex composed of the recently characterized PAK interacting partner PIX (PAK-interacting guanine nucleotide exchange factor) and its tightly associated p95 protein. PAK and PIX-p95 appear to be differentially activated and phosphorylated depending on the intracellular environment in which nef is expressed. These results identify the PLY-p95 complex as a novel effector of Nef in primary cells and suggest that the regulation of the PAK signaling pathway may differ in T cells and macrophages.
机构:
Glaxo Wellcome Inc, Med Res Ctr, Immunopathol Unit, Stevenage SG1 2NY, Herts, EnglandGlaxo Wellcome Inc, Med Res Ctr, Immunopathol Unit, Stevenage SG1 2NY, Herts, England
Bell, I
Ashman, C
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Glaxo Wellcome Inc, Med Res Ctr, Immunopathol Unit, Stevenage SG1 2NY, Herts, EnglandGlaxo Wellcome Inc, Med Res Ctr, Immunopathol Unit, Stevenage SG1 2NY, Herts, England
Ashman, C
Maughan, J
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Glaxo Wellcome Inc, Med Res Ctr, Immunopathol Unit, Stevenage SG1 2NY, Herts, EnglandGlaxo Wellcome Inc, Med Res Ctr, Immunopathol Unit, Stevenage SG1 2NY, Herts, England
Maughan, J
Hooker, E
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Glaxo Wellcome Inc, Med Res Ctr, Immunopathol Unit, Stevenage SG1 2NY, Herts, EnglandGlaxo Wellcome Inc, Med Res Ctr, Immunopathol Unit, Stevenage SG1 2NY, Herts, England
Hooker, E
Cook, F
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Glaxo Wellcome Inc, Med Res Ctr, Immunopathol Unit, Stevenage SG1 2NY, Herts, EnglandGlaxo Wellcome Inc, Med Res Ctr, Immunopathol Unit, Stevenage SG1 2NY, Herts, England
Cook, F
Reinhart, TA
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Glaxo Wellcome Inc, Med Res Ctr, Immunopathol Unit, Stevenage SG1 2NY, Herts, EnglandGlaxo Wellcome Inc, Med Res Ctr, Immunopathol Unit, Stevenage SG1 2NY, Herts, England
机构:Univ Calif San Francisco, Gladstone Inst Virol & Immunol, San Francisco, CA 94141 USA
Bresnahan, PA
Yonemoto, W
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机构:Univ Calif San Francisco, Gladstone Inst Virol & Immunol, San Francisco, CA 94141 USA
Yonemoto, W
Ferrell, S
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机构:Univ Calif San Francisco, Gladstone Inst Virol & Immunol, San Francisco, CA 94141 USA
Ferrell, S
Williams-Herman, D
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机构:Univ Calif San Francisco, Gladstone Inst Virol & Immunol, San Francisco, CA 94141 USA
Williams-Herman, D
Geleziunas, R
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机构:Univ Calif San Francisco, Gladstone Inst Virol & Immunol, San Francisco, CA 94141 USA
Geleziunas, R
Greene, WC
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Univ Calif San Francisco, Gladstone Inst Virol & Immunol, San Francisco, CA 94141 USAUniv Calif San Francisco, Gladstone Inst Virol & Immunol, San Francisco, CA 94141 USA
机构:
Glaxo Wellcome Inc, Med Res Ctr, Immunopathol Unit, Stevenage SG1 2NY, Herts, EnglandGlaxo Wellcome Inc, Med Res Ctr, Immunopathol Unit, Stevenage SG1 2NY, Herts, England
Bell, I
Ashman, C
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机构:
Glaxo Wellcome Inc, Med Res Ctr, Immunopathol Unit, Stevenage SG1 2NY, Herts, EnglandGlaxo Wellcome Inc, Med Res Ctr, Immunopathol Unit, Stevenage SG1 2NY, Herts, England
Ashman, C
Maughan, J
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Glaxo Wellcome Inc, Med Res Ctr, Immunopathol Unit, Stevenage SG1 2NY, Herts, EnglandGlaxo Wellcome Inc, Med Res Ctr, Immunopathol Unit, Stevenage SG1 2NY, Herts, England
Maughan, J
Hooker, E
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Glaxo Wellcome Inc, Med Res Ctr, Immunopathol Unit, Stevenage SG1 2NY, Herts, EnglandGlaxo Wellcome Inc, Med Res Ctr, Immunopathol Unit, Stevenage SG1 2NY, Herts, England
Hooker, E
Cook, F
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Glaxo Wellcome Inc, Med Res Ctr, Immunopathol Unit, Stevenage SG1 2NY, Herts, EnglandGlaxo Wellcome Inc, Med Res Ctr, Immunopathol Unit, Stevenage SG1 2NY, Herts, England
Cook, F
Reinhart, TA
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h-index: 0
机构:
Glaxo Wellcome Inc, Med Res Ctr, Immunopathol Unit, Stevenage SG1 2NY, Herts, EnglandGlaxo Wellcome Inc, Med Res Ctr, Immunopathol Unit, Stevenage SG1 2NY, Herts, England
机构:Univ Calif San Francisco, Gladstone Inst Virol & Immunol, San Francisco, CA 94141 USA
Bresnahan, PA
Yonemoto, W
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机构:Univ Calif San Francisco, Gladstone Inst Virol & Immunol, San Francisco, CA 94141 USA
Yonemoto, W
Ferrell, S
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h-index: 0
机构:Univ Calif San Francisco, Gladstone Inst Virol & Immunol, San Francisco, CA 94141 USA
Ferrell, S
Williams-Herman, D
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h-index: 0
机构:Univ Calif San Francisco, Gladstone Inst Virol & Immunol, San Francisco, CA 94141 USA
Williams-Herman, D
Geleziunas, R
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h-index: 0
机构:Univ Calif San Francisco, Gladstone Inst Virol & Immunol, San Francisco, CA 94141 USA
Geleziunas, R
Greene, WC
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h-index: 0
机构:
Univ Calif San Francisco, Gladstone Inst Virol & Immunol, San Francisco, CA 94141 USAUniv Calif San Francisco, Gladstone Inst Virol & Immunol, San Francisco, CA 94141 USA