The serine proteinase GZMB is crucial for the rapid induction of target cell apoptosis by cytotoxic T cells. GZMB enters cells in a perforin-independent manner, predicting the existence of a cell surface receptor(s). Motyka et al. (2000) presented evidence that this receptor is the cation-independent mannose 6-phosphate receptor (CIMPR), also called IGF2R (147280).
NCBI Summary:
Cytolytic T lymphocytes (CTL) and natural killer (NK) cells share the remarkable ability to recognize, bind, and lyse specific target cells. They are thought to protect their host by lysing cells bearing on their surface 'nonself' antigens, usually peptides or proteins resulting from infection by intracellular pathogens. The protein encoded by this gene is crucial for the rapid induction of target cell apoptosis by CTL in cell-mediated immune response. [provided by RefSeq, Jul 2008]
General function
Ligand, Enzyme
Comment
Cellular localization
Secreted
Comment
Increased levels of serum granzyme-B is associated with insulin resistance and increased cardiovascular risk in adolescent polycystic ovary syndrome patients. Oztas E et al. (2016) Our aim was to determine serum perforin and granzyme-B levels in adolescent PCOS patients, and to investigate whether they are associated with some of the insulin sensitivity, obesity and cardiovascular (CV) risk markers and metabolic syndrome. A case-control study was carried out including a total of 172 adolescents (83 PCOS patients and 89 age-matched healthy controls). Participants were recruited consecutively. Homeostasis model assessment (HOMA-IR), lipid parameters, and anthropometric measurements were determined. Serum perforin and granzyme B levels were measured by commercially available ELISA kits. HOMA-IR>3.16 was considered to indicate the presence of insulin resistance. Logistic regression analysis was applied for the predictive value of granzyme-B for increased CV risk in PCOS patients. As body mass index (BMI) of the PCOS patients was significantly higher than the controls (median 24.6kg/m(2) and 21.4kg/m(2), respectively, p<0.001) all parameters were evaluated after adjustment for BMI. Adolescents with PCOS had significantly higher levels of fasting glucose, insulin, HOMA-IR and granzyme-B when compared with controls. According to the results of logistic regression analysis, granzyme-B levels were found to be significantly associated with increased HOMA-IR (OR=6.120, 95% CI: 2.352-15.926, p<0.001) in adolescent PCOS patients. Additionally, elevated levels of serum granzyme-B were predictive for increased CV risk in PCOS patients (OR=0.237, 95% CI: 0.091-0.616, p=0.003). Increased levels of serum granzyme-B are independently associated with insulin resistance and also with increased CV risk in adolescent polycystic ovary syndrome patients.//////////////////
Ovarian function
Follicle development
Comment
Expression regulated by
FSH
Comment
Ovarian localization
Granulosa
Comment
Sasson R, et al 2003 reported novel genes modulated by FSH in normal and immortalized FSH-responsive
cells and new insights into the mechanism of FSH action.
Follicle-stimulating hormone (FSH) controls the development of follicle-enclosed oocytes in the
mammalian ovary by interacting with specific receptors located exclusively on granulosa cells. Its
biological activity involves stimulation of intercellular communication, intracellular signaling, and
up-regulation of steroidogenesis; the entire spectrum of genes regulated by FSH is not yet fully
characterized. The authors have established monoclonal rat FSH-responsive granulosa cell lines that
express FSH receptors at 20-fold higher rates than with primary cells, and thus increased the
probability of yielding a distinct spectrum of genes modulated by FSH. Using Affymetrix DNA
microarrays, they discovered 11 genes not reported earlier to be up-regulated by FSH and 9 genes
not reported earlier to be down-regulated by FSH. Modulation of signal transduction associated
with G-protein signaling, phosphorylation of proteins, and intracellular-extracellular ion balance
was suggested by up-regulation of decay accelerating factor GPI-form precursor (DAF), membrane
interacting protein RGS16, protein tyrosine phosphatase (PTPase), oxidative stress-inducible protein tyrosine phosphatase (OSIPTPase), and down-regulation of rat prostatic acid phosphatase
(rPAP), Na+, K+-ATPase, and protein phosphatase 1beta. Elevation in granzyme-like proteins 1
and 3, and natural killer (NK) cell protease 1 (NKP-1) along with reduction in carboxypeptidase E
indicates possible FSH-mediated preparation of the cells for apoptosis.