Identifiers
HUGO:PRF1
Maps_Modules
HMC:AVOIDING_IMMUNE_DESTRUCTION
Adaptive Immune Response / TCR_SIGNALING
References
PMID:7520535
NATURAL_KILLER
CASCADE:MIF
CASCADE:LFA1
CASCADE:IL12
CASCADE:IL2
CASCADE:IL15
CASCADE:IFNAB
PMID:21350056, PMID:23906377
Human perforin is expressed in natural killer cells.NK cytotoxicity is mediated by the directed exocytosis of cytolytic granules to release perforins and granzymes, which perforate the target cell plasma cell membrane and trigger apoptosis, respectively.
PMID:11062502, PMID:15536084
ERK1/2 activation induces perforin and granzyme B movement towards target tumor cells downstream of PI3K signaling in NK cells.
PMID:16204312
Calcium influx is an early event during perforin-mediated cytotoxicity. PLC-??2 is absolutely required to regulate degranulation of cytotoxic perforin granules.
PMID:15356110
ICAM1 assosiation with LAF-1 provides NK cell cytotoxicity
via polarization of perforin cytotoxic granules. This signaling is
very sensitive to inhibition of actin polymerization by cytochalasin D, of Src family tyrosine kinases by PP1, and was partially sensitive to inhibition of PI3K by wortmannin.
LFA-1-dependent cytotoxicity is sensitive to inhibition by killer cell Ig-like receptors ( CD158a and CD158b).
PMID:15113754
LFA-1 signaling through p44/42 is coupled to perforin degranulation in CD56+CD8+ natural killer cells.
(ICAM-2) and ICAM-3 promoted LFA-1-directed perforin release, whereas ICAM-1 had little effect.
PMID:9637476, PMID:10878343
MIF prevented the release of perforin granules by NK cells but not CTLs.
Tumor cells produce Macrophage Migration-Inhibitory Factor to Prevent Lysis by NK Cells.
→ PRF1@default
→ TUMOR_KILING@TUMOR_CELL_AS_EFFECTOR
→ PRF1@SECRETORY_GRANULE