Identifiers
HUGO:GZMB
granzyme B (granzyme 2, cytotoxic T-lymphocyte-associated serine esterase 1)
HUGO:GZMB HGNC:4709 ENTREZ:3002 UNIPROT:P10144
Maps_Modules
HMC:AVOIDING_IMMUNE_DESTRUCTION
Adaptive Immune Response / TCR_SIGNALING
HMC:RESISTING_CELL_DEATH
Regulated Cell Death / APOPTOSIS
Regulated Cell Death / MOMP_REGULATION
References
PMID:14499263 PMID:8432729
CASCADE:NKG2D
CASCADE:2B4
CASCADE:IL15
NATURAL_KILLER
PMID:16106370, PMID:15607806
Five granzymes are expressed in human NK cells (Grz A, B, H, K and M)
GrzA and GrzK are trypsins (cleaving at basic residues arginine and lysine)
GrzB is an aspase, cleaving after aspartic acid residues, and GrzH is a chymase, cleaving after hydrophobic residues such as phenylalanine.
GrzM has a unique enzyme specificity, preferring cleavage after methionine, leucine, or isoleucine.
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:20189481
NKG2D, 2B4 signalings induces Granzyme B release probaly via VAV1/ERK pathway
PMID:24795729
PI3K???AKT???mTOR pathway is required for granzyme B production downstream of IL15.
PMID:24248158
Hypoxia-induced autophagy impairs breast cancer cell susceptibility to NK-mediated lysis and that this impairment is reverted by targeting autophagy. We provide evidence that activation of autophagy in hypoxic cells is involved in selective degradation of the pro-apoptotic NK-derived serine protease GZMB/granzyme B, thereby blocking NK-mediated target cell apoptosis. Our in vivo data validate the concept that targeting autophagy in cancer cells promotes tumor regression by facilitating their elimination by NK cells.
PMID:18287025
JNK pathway plays important role in NK activation.JNK induces assosiation of Paxilin with MTOC resulted in polarization of the MTOC and cytolytic granules, and finally exocytosis of cytolytic proteins downstream of NKG2D. Inhibition of JNK activity by D-JNK-1, SP600125, or JNK-1-specific siRNA blocked polarization of granzyme B
Maps_Modules
HMC:RESISTING_CELL_DEATH
Regulated Cell Death / APOPTOSIS
Regulated Cell Death / MOMP_REGULATION
References
rc_re42( Regulated Cell Death ):
influenceDelete: reactants to re
we consider only that CASP3 or GZMB activity can influence Bax recruitment to membrane, not the fact that MCL1 increases it
hierarchical:post-MOMP
reactionType:proteases.cleavage
PMID:15713684
in different human cancer cell lines by Granzyme B
PMID:15637055
in Jurkat leukemia T cells, by CASP3 upon TRAIL-induced apoptosis
rc_re508( Regulated Cell Death ):
PMID:9727492
in vitro cleavage of BID by CASP8 and GZMB, BID poor substrate for CASP3
in Jurkat cleavage of BID by CASP8 upon Fas stimulation
in Hela exposed to TNF+CHX cleavage of BID by CASP8
PMID:10805722
in vitro cleavage of in vitro translated BID by purified granzyme B
in Jurkat cells exposed to GZMB+adenovirus, BID cleavage occurs independently of caspases (zVAD-fmk)
PMID:11085743
in Jurkat cells exposed to GZMB+perforin, Bcl2 over-expression mediated cell protection is abrogated by over-over-expression of BID (wt or CASP8-uncleavable mutant) but of D75 (GZMB in vitro cleavage site) mutant
PMID:11085742
in Jurkat cells exposed to GZMB+adenovirus+zVAD-fmk, BID is cleaved and localizes to mitochondria
PMID:10364179
cleavage of BID by CASP8 and CASP3
PMID:11832478
in vitro by CASP2
rc_re513( Regulated Cell Death ):
PMID:11583622
in vitro, phosphorylation of BID has no effect on Granzyme B mediated cleavage
rc_re1242( Regulated Cell Death ):
PMID:11287608
in 32D murine cells, upon IL3 withdrawal, BAD cleavage
in vitro cleavage of BAD by recombinant CASP 2,3,7,8,10, and GZMB
Maps_Modules
HMC:RESISTING_CELL_DEATH
Regulated Cell Death / APOPTOSIS
Regulated Cell Death / MOMP_REGULATION