Structure and Function of Perforin

Podack, Eckhard R.; Olsen, Kristin J.; Lowrey, David M.; Lichtenheld, Mathias G.

doi:10.1007/978-3-642-73911-8_2

Cited by 21 publications

(11 citation statements)

References 28 publications

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“…Sequential binding of C7, C8 and multiple C9 molecules to this preliminary C5bC6 complex leads to the formation of a porous transmembrane structure (MAC) that is inserted into the lipid membrane and causes cytolysis. Complement factors C6 to C9 are ancestrally related and are structurally similar to perforin, a lytic protein of natural killer cells and cytotoxic T cells [47]. The human components share common structural motifs, such as thrombospondin, low-density lipoprotein receptor, and epidermal growth factor precursor domains [48].…”

Section: The Components Of the Lytic Pathwaymentioning

confidence: 99%

The complement system in teleosts

Holland

Lambris

2002

Fish & Shellfish Immunology

542

251

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Section: The Components Of the Lytic Pathwaymentioning

confidence: 99%

The complement system in teleosts

Holland

Lambris

2002

Fish & Shellfish Immunology

542

251

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“…Biochemical analysis of the most abundant molecules stored in these secretory organelles has revealed the presence of perforin/cytolysin, a family of serine esterases (the granzymes), proteoglycans, calreticulin, and several lysosomal enzymes (10)(11)(12). Among the granule proteins, the only one with an unequivocal lytic character is perforin, a pore-forming protein with high structural and functional homology with the lytic complement proteins (13)(14)(15). Experiments using antisense oligonucleotides and perforin-knockout mice have revealed its crucial role in cytolysis (16,60,61).…”

mentioning

confidence: 99%

Granzyme A released upon stimulation of cytotoxic T lymphocytes activates the thrombin receptor on neuronal cells and astrocytes.

Suidan

Bouvier

Schaerer

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

119

104

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Granzymes are a family of serine proteases that are harbored in cytoplasmic granules of activated T lymphocytes and are released upon target cell interaction. Immediate and complete neurite retraction was induced in a mouse neuronal cell line when total extracts of granule proteins were added. This activity was isolated and identified as granzyme A. This protease not only induced neurite retraction at nanomolar concentrations but also reversed the stellation of astrocytes. Both effects were critically dependent on the esterolytic activity of granzyme A. As neurite retraction is known to be induced by thrombin, possible cleavage and activation of the thrombin receptor were investigated. A synthetic peptide spanning the N-terminal thrombin receptor activation sequence was cleaved by granzyme A at the authentic thrombin cleavage site Leu-Asp-Pro-Arg -Ser. Antibodies to the thrombin receptor inhibited both thrombin and granzyme A-mediated neurite retraction. Thus, T-cell-released granzyme A induces cellular responses by activation of the thrombin receptor. As braininfiltrating CD4+ lymphocytes are the effector cells in experimental allergic encephalomyelitis, granzyme A released in the brain may contribute to the etiology of autoimmune disorders in the nervous system.

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“…In the presence of Ca 2+ , perforin binds to the cell membrane, penetrates its lipid bilayer, and polymerizes, forming a pore approximately 16 nm in diameter (Podack et al, 1989), which facilitates the entry of proteolytic enzymes into the target cell.…”

Section: Phenomenon and Pathways Of Activation Of Apoptosismentioning

confidence: 99%

Role of proteases in activation of apoptosis

1997

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Programmed cell death, or apoptosis, is a physiological cell suicide mechanism, which is triggered in the cells by different stimuli. It has been shown that proteases play a significant role both in the target cell killing by cytotoxic lymphocytes and in the TNF-or anti-Fas-induced cell death. The proteases involved in the early (induction) and late (cell self-destruction) stages of apoptosis are reviewed. It is suggested that the late stages are connected with the activation of a cascade of intracellular proteases, which leads to massive protein destruction. It is likely that the protein destruction is mainly designed for preventing autoimmune response to proteins released from dying cells.

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Structure and Function of Perforin

Cited by 21 publications

References 28 publications

The complement system in teleosts

The complement system in teleosts

Granzyme A released upon stimulation of cytotoxic T lymphocytes activates the thrombin receptor on neuronal cells and astrocytes.

Role of proteases in activation of apoptosis

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