Abstract
Focal adhesion plaques were severely affected in human embryonic fibroblasts permeabilized with digitonin and incubated in buffer containing the human immunodeficiency virus type 1 protease (HIV-1 PR). A mutant HIV-1 PR (3271 HIV-1 PR) had no effect on focal adhesion plaques. Similar effects were seen with cells microinjected with either HIV-1 PR or 3271 HIV-1 PR. Immunoblots of the human embryonic fibroblasts demonstrated that a number of focal adhesion plaque proteins were specifically cleaved by HIV-1 PR. These included fimbrin, focal adhesion plaque kinase (FAK), talin, and, to a lesser extent, filamin, spectrin and fibronectin. Proteins detected by antibodies to beta 4 integrin and alpha 3 integrin were also cleaved by the HIV-1 PR. Control experiments demonstrated that the effect and protein cleavages described are due to action of the HIV-1 PR and not to the action of endogenous host cell proteases.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Actin Cytoskeleton / metabolism
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Animals
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Cell Adhesion / drug effects
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Cell Adhesion / physiology*
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Cell Membrane / drug effects
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Cell Membrane / metabolism*
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Cells, Cultured
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Extracellular Matrix / drug effects
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Extracellular Matrix / metabolism*
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Fetus
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Fibroblasts / drug effects
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Fibroblasts / metabolism*
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Focal Adhesion Kinase 1
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Focal Adhesion Protein-Tyrosine Kinases
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Focal Adhesions / drug effects
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Focal Adhesions / metabolism*
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HIV Infections / metabolism*
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HIV Infections / physiopathology
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HIV Protease / genetics
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HIV Protease / metabolism*
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HIV Protease / pharmacology
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Humans
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Membrane Glycoproteins / drug effects
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Membrane Glycoproteins / metabolism
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Mice
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Microfilament Proteins*
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Mutation / physiology
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Protein-Tyrosine Kinases / drug effects
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Protein-Tyrosine Kinases / metabolism
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Talin / drug effects
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Talin / metabolism
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Vimentin / drug effects
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Vimentin / metabolism
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Vinculin / drug effects
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Vinculin / metabolism
Substances
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Membrane Glycoproteins
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Microfilament Proteins
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Talin
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Vimentin
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plastin
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Vinculin
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Protein-Tyrosine Kinases
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Focal Adhesion Kinase 1
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Focal Adhesion Protein-Tyrosine Kinases
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PTK2 protein, human
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Ptk2 protein, mouse
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HIV Protease