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- Table of Contents
Facts about Serine/threonine-protein kinase STK11.
Also phosphorylates non- AMPK family proteins such as STRADA, PTEN and maybe p53/TP53. Acts as a key upstream regulator of AMPK by mediating phosphorylation and activation of AMPK catalytic subunits PRKAA1 and PRKAA2 and thereby regulates processes including: inhibition of signaling pathways that promote cell growth and proliferation when energy levels are low, glucose homeostasis in liver, activation of autophagy when cells undergo nutrient deprivation, and B-cell differentiation in the germinal centre in response to DNA damage.
Human | |
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Gene Name: | STK11 |
Uniprot: | Q15831 |
Entrez: | 6794 |
Belongs to: |
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protein kinase superfamily |
EC 2.7.11.1; LKB1 serine/threonine kinase 11 (Peutz-Jeghers syndrome); LKB1; PJS polarization-related protein LKB1; PJS; Renal carcinoma antigen NY-REN-19; serine/threonine kinase 11; serine/threonine-protein kinase 11; Serine/threonine-protein kinase LKB1; STK11
Mass (kDA):
48.636 kDA
Human | |
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Location: | 19p13.3 |
Sequence: | 19; NC_000019.10 (1205778..1228431) |
Ubiquitously expressed. Strongest expression in testis and fetal liver.
Nucleus. Cytoplasm. Membrane. Mitochondrion. A small fraction localizes at membranes (By similarity). Relocates to the cytoplasm when bound to STRAD (STRADA or STRADB) and CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta). Translocates to the mitochondrion during apoptosis. Translocates to the cytoplasm in response to metformin or peroxynitrite treatment. PTEN promotes cytoplasmic localization.; [Isoform 2]: Nucleus. Cytoplasm. Predominantly nuclear, but translocates to the cytoplasm in response to metformin or peroxynitrite treatment.
When you're looking for antibodies that target STK11, Boster has the solution. They offer primary antibodies that have been validated on Western Blotting, Immunohistochemistry, and ELISA. Boster's primary antibodies are made from recombinant polypeptides or proteins that represent a specific epitope on the antigen. This allows you to use the same antibody to study a wide variety of samples.
The STK11 marker has been identified as a promising candidate for next-generation sequencing of non-small cell lung cancer. This marker helps to differentiate mucinous adenocarcinomas of the uterus from other adenocarcinomas. Furthermore, STK11 mutations can help in predicting the response to a particular chemotherapy regimen, including immune checkpoint inhibitors (ICIs).
In one study, researchers identified a link between STK11 mutations and poor survival in non-squamous NSCLC patients. Furthermore, STK11/TP53 comutations are associated with longer OS. The STK11/HPD association was also discovered in a recent study in patients with HPD. Among three patients with HPD, STK11-mutated tumors had poor response rates to ICIs and shorter median PFS and OS.
Although STK11 gene mutations are extremely rare in sporadic MDA, their presence in other cancer types makes it difficult to perform hot-spot testing. Fortunately, plasma-derived tumor genetic material is an excellent source of DNA for NGS analysis. This method can identify mutations in the STK11 gene in high-risk cancers. And because it's so widespread, it also offers the possibility of using plasma as a source for tumor genetic material.
Mutations in exons 1-2 of the STK11 gene result in oncogenic activity. Mutations in exons three to nine may impair the function of the gene. The STK11 gene is a valuable marker for cancer patients. The STK11 gene has a wide range of functions, including oncogenic, tumor suppressor and immune-suppressor activities.
Using the STK11 gene as a marker allows the analysis of protein expression in samples from bovine adipocytes. This marker binds to a region in the cDNA coding for the STK11 gene, and is highly specific to the protein. To perform this analysis, we used the cDNA synthesized from bovine perirenal and groin fat tissues. Using a gene-specific inner and outer primers, we generated cDNAs that contained the coding sequence of STK11 (Figure S1).
We performed Western Blotting with the STK11 marker to identify the protein of interest. We used three different cell lines - A549) and NCI-h2975 - to analyze FAM117A expression. The internal control was b-actin. This quantitative analysis enabled us to evaluate a variety of proteins at the protein level. Lastly, we confirmed the presence of phosphorylated STK11 protein in lung cancer cell lines.
Following cDNA preparation, the STK11-recovered cell lines were cultured in the same medium containing 0.05% PBST. We then seeded the cells in a 6-well culture plate, 13 x 105 per well. After five days, the cells were allowed to differentiate into a monolayer. To visualize the bands, we used an enhanced chemiluminescence detection system and a LA3000 luminescence image analyzer. The antibodies were purchased from Cell Signaling, Santa Cruz, and BioLegend.
The STK11 gene is involved in regulation of fat cell development in various animal models. The phosphorylation of STK11 may affect the development of mature adipocytes. Further studies are needed to examine the role of STK11 in fat cell development and function. However, we can't overlook the role of LKB1 in these studies. The following are some of the studies that show the importance of the STK11 gene.
STK11/LKB1 is a highly conserved serine/threonine kinase that is involved in cellular energy metabolism. It also plays a role in the mTOR pathway and protein synthesis. Mutations in STK11 are associated with tumor-extrinsic functions and an inert immune microenvironment. Mutated STK11 tumors have reduced densities of cytotoxic CD8+ T lymphocytes.
The STK11/LKB1 marker is a master upstream kinase that regulates the AMPK pathway. It promotes autophagy and mitophagy, which are metabolic processes that occur in cells in response to nutrient deprivation. By increasing NADPH production, the STK11/LKB1 pathway protects the genome from oxidative damage and promotes cell survival.
Although STK11/LKB1 mutations have no proven impact on therapeutic strategy, exploratory analyses suggest that ICI should be used in first-line settings for all patients with NSCLC with a genetically-defined risk of oncogenic addiction. It may also influence response prediction algorithms or decisions on adding chemotherapy. But more research is needed to know exactly how the STK11/LKB1 marker affects cancer cells and their response to treatment.
STK11 mutations affect the immune microenvironment of NSCLC. Immunoprofile analysis of 221 untreated resected LUAD tumors demonstrated that STK11-mutant tumors had a higher neutrophil count, lower CD8+ T cells, and lower dendritic cells. Furthermore, STK11-mutant tumors displayed a lower expression of PD-L1. Interestingly, the KRAS mutation was not implicated in the modulation of the tumor immune microenvironment.
The best method to detect STK11 mutations is comprehensive next-generation sequencing, which uses tissue obtained from a biopsy to look for a high number of biomarkers simultaneously. Liquid biopsies are also an option if patients cannot undergo a biopsy. They can also check for STK11 in blood. Patients who cannot undergo a biopsy should ask their doctor about the use of liquid biopsy for STK11 mutations.
A new ELISA with an STK11 marker from Boster Bio is designed for tumors expressing this protein. The results will allow physicians to determine whether patients are harboring the mutated form of STK11. The tumor status may influence the course of treatment. For example, patients with cancer that express STK11 or LKB1 are likely to be more responsive to antiangiogenic therapies.
ELISAs can be complicated and require choices at nearly every step of the experiment. From sample preparation to the choice of blocking buffer, there are many variables to consider. Fortunately, Boster's technical blog offers tips for optimizing your ELISA and answering common questions. These blogs also include articles on fundamental principles and protocols and provide recommended products and reagents for various types of experiments.
An ELISA using the STK11 marker by Boster Bio is designed to detect the level of this protein in human blood and serum. The STK11/LKB1 protein is located on chromosome 19p13.3. It is a master upstream kinase that regulates glucose and lipid metabolism, cellular functions, and polarity. When AMPK is activated, it causes various reactions, including autophagy and cell death.
The STK11 mutation is one of many genetic alterations that impact the immune microenvironment. In the MSK-IMPACT cohort, 240 NSCLC patients were studied for the effects of gene alterations on response to chemotherapy. Patients with STK11 mutations were associated with higher neutrophil counts, lower CD8+ T cell counts, lower dendritic cells, and decreased PD-L1 expression. Interestingly, the KRAS mutation was not implicated in the regulation of the tumor immune microenvironment.
Recent studies have demonstrated that patients with tumors harboring STK11 mutations had significantly lower overall response rates and shorter median PFS and OS compared with patients with unmutated KRAS. Additionally, bi-allelic disruption of STK11 caused tumors to become resistant to immunotherapy. Therefore, drugs targeting STK11 mutations are highly promising for treating cancer. However, the current data suggest that drugs targeting this mutation should be used cautiously.
These drugs target mutations in STK11, a gene responsible for tumor suppression. Mutations in STK11 lead to the loss of regulatory functions of AMPK, which in turn impairs mTOR and HIF-1-a signaling pathways. While these agents may not yet be available to the public, the results of ongoing clinical trials are promising and offer hope to patients with tumors harboring the mutation. Because these tumors are often refractory to immune therapies, physicians should consider their experience and expertise when prescribing drugs for patients with STK11 mutations.
Researchers from Boster Bio have identified an improved way to detect and treat tumors harboring STK11 mutations. The new compounds, called PD-L1 inhibitors, can block PD-L1 receptors. PD-L1 inhibitors have also been found to increase T-cell activity in tumors harboring STK11 mutations. But, the results of these new drugs should only be seen in the next few years.
In addition to these hematologic tests, antisense oligonucleotides, which generate hypersensitive platelets, may also help prevent tumors from growing. The study authors, including Zhang and Zhao, describe their experience with patients and discuss their findings. The study also highlights the need for further trials and development of the new drugs. The results are promising, and patients may soon be treated without any side effects.
PMID: 9425897 by Jenne D.E., et al. Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase.
PMID: 9537235 by Bignell G.R., et al. Low frequency of somatic mutations in the LKB1/Peutz-Jeghers syndrome gene in sporadic breast cancer.
*More publications can be found for each product on its corresponding product page