SDS-PAGE
(The purity was determined to be >90% by densitometry. Approx. MW 85 kDa)
LKB1(STK11) recombinant protein
LKB1 (STK11) recombinant protein
Shipping: Dry Ice.
SDS-PAGE
(The purity was determined to be >90% by densitometry. Approx. MW 85 kDa)
SDS-PAGE
(The purity was determined to be >90% by densitometry. Approx. MW 85 kDa)
Scientific Background: LKB1(STK11) is a member of the serine/threonine kinase family which regulates cell polarity and functions as a tumor suppressor. STK11 is a critical barrier to pulmonary tumorigenesis which controlling initiation, differentiation, and metastasis. STK11 plays a central role in restricting HSC entry into cell cycle and in broadly maintaining energy homeostasis in hematopoietic cells through a novel metabolic checkpoint (1). STK11 serves as an essential regulator of HSCs and hematopoiesis, and more generally, points to the critical importance of coupling energy metabolism and stem cell homeostasis (2).
2. Gan, B.et.al: Lkb1 regulates quiescence and metabolic homeostasis of haematopoietic stem cells. Nature 468: 701-704, 2010.
NCBI and Uniprot Product Information
NCBI Description
This gene, which encodes a member of the serine/threonine kinase family, regulates cell polarity and functions as a tumor suppressor. Mutations in this gene have been associated with Peutz-Jeghers syndrome, an autosomal dominant disorder characterized by the growth of polyps in the gastrointestinal tract, pigmented macules on the skin and mouth, and other neoplasms. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized. [provided by RefSeq, Jul 2008]
Uniprot Description
Function: Tumor suppressor serine/threonine-protein kinase that controls the activity of AMP-activated protein kinase (AMPK) family members, thereby playing a role in various processes such as cell metabolism, cell polarity, apoptosis and DNA damage response. Acts by phosphorylating the T-loop of AMPK family proteins, leading to promote their activity: phosphorylates PRKAA1, PRKAA2, BRSK1, BRSK2, MARK1, MARK2, MARK3, MARK4, NUAK1, NUAK2, SIK1, SIK2, SIK3 and SNRK but not MELK. Also phosphorylates non-AMPK family proteins such as STRADA and possibly p53/TP53. Acts as a key upstream regulator of AMPK by mediating phosphorylation and activation of AMPK catalytic subunits PRKAA1 and PRKAA2: it thereby regulates 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, B-cell differentiation in the germinal center in response to DNA damage. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton. Required for cortical neurons polarization by mediating phosphorylation and activation of BRSK1 and BRSK2, leading to axon initiation and specification. Involved in DNA damage response: interacts with p53/TP53 and recruited to the CDKN1A/WAF1 promoter to participate in transcription activation. Able to phosphorylate p53/TP53; the relevance of such result in vivo is however unclear and phosphorylation may be indirect and mediated by downstream STK11/LKB1 kinase NUAK1 Also acts as a mediator p53/TP53-dependent apoptosis via interaction with p53/TP53: translocates to mitochondrion during apoptosis and regulates p53/TP53-dependent apoptosis pathways. Ref.10 Ref.12 Ref.13 Ref.14 Ref.15 Ref.17 Ref.18 Ref.28
Catalytic activity: ATP + a protein = ADP + a phosphoprotein. Ref.15
Cofactor: Magnesium or Manganese.
Enzyme regulation: Activated by forming a complex with STRAD (STRADA or STRADB) and CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta): STRADA (or STRADB)-binding promotes a conformational change of STK11/LKB1 in an active conformation, which is stabilized by CAB39/MO25alpha (or CAB39L/MO25beta) interacting with the STK11/LKB1 activation loop. Sequestration in the nucleus by NR4A1 prevents it from phosphorylating and activating cytoplasmic AMPK. Ref.31 Ref.32
Subunit structure: Catalytic component of a trimeric complex composed of STK11/LKB1, STRAD (STRADA or STRADB) and CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta): the complex tethers STK11/LKB1 in the cytoplasm and stimulates its catalytic activity. Found in a ternary complex composed of SMAD4, STK11/LKB1 and STK11IP. Interacts with p53/TP53, SMAD4, STK11IP and WDR6. Interacts with NR4A1. Ref.9 Ref.12 Ref.13 Ref.18 Ref.19 Ref.31
Subcellular location: Nucleus. Cytoplasm. Membrane
By similarity. Mitochondrion. Note: 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 mitochondrion during apoptosis. Ref.10 Ref.12 Ref.13 Ref.18 Ref.24 Ref.31
Tissue specificity: Ubiquitously expressed. Strongest expression in testis and fetal liver.
Post-translational modification: Phosphorylated by ATM at Thr-363 following ionizing radiations (IR). Phosphorylation at Ser-428 by RPS6KA1 and/or some PKA is required to inhibit cell growth. Phosphorylation at Ser-428 is also required during neuronal polarization to mediate phosphorylation of BRSK1 and BRSK2
By similarity. Ref.10 Ref.12 Ref.24
Involvement in disease: Peutz-Jeghers syndrome (PJS) [MIM:175200]: An autosomal dominant disorder characterized by melanocytic macules of the lips, multiple gastrointestinal hamartomatous polyps and an increased risk for various neoplasms, including gastrointestinal cancer.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.36 Ref.38 Ref.40 Ref.45 Ref.48Testicular germ cell tumor (TGCT) [MIM:273300]: A common malignancy in males representing 95% of all testicular neoplasms. TGCTs have various pathologic subtypes including: unclassified intratubular germ cell neoplasia, seminoma (including cases with syncytiotrophoblastic cells), spermatocytic seminoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma, and teratoma.Note: The gene represented in this entry may be involved in disease pathogenesis. Ref.33 Ref.41Defects in STK11 are associated with some sporadic cancers, especially lung cancers. Frequently mutated and inactivated in non-small cell lung cancer (NSCLC). Defects promote lung cancerigenesis process, especially lung cancer progression and metastasis. Confers lung adenocarcinoma the ability to trans-differentiate into squamous cell carcinoma. Also able to promotes lung cancer metastasis, via both cancer-cell autonomous and non-cancer-cell autonomous mechanisms.
Sequence similarities: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. LKB1 subfamily.Contains 1 protein kinase domain.
Research Articles on LKB1(STK11)
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Product Notes
The LKB1(STK11) stk11 (Catalog #AAA515310) is a Recombinant Protein produced from Sf9 insect cells and is intended for research purposes only. The product is available for immediate purchase. The tag for this protein is GST tag!!Expression System||Sf9 insect cells using baculovirus!!Source Note||Recombinant full-length human LKB1(STK11) was expressed by baculovirus in Sf9 insect cells. AAA Biotech's LKB1(STK11) can be used in a range of immunoassay formats including, but not limited to, Kinase Assay, Western Blot (WB). Researchers should empirically determine the suitability of the LKB1(STK11) stk11 for an application not listed in the data sheet. Researchers commonly develop new applications and it is an integral, important part of the investigative research process. It is sometimes possible for the material contained within the vial of "LKB1(STK11), Recombinant Protein" to become dispersed throughout the inside of the vial, particularly around the seal of said vial, during shipment and storage. We always suggest centrifuging these vials to consolidate all of the liquid away from the lid and to the bottom of the vial prior to opening. Please be advised that certain products may require dry ice for shipping and that, if this is the case, an additional dry ice fee may also be required.Precautions
All products in the AAA Biotech catalog are strictly for research-use only, and are absolutely not suitable for use in any sort of medical, therapeutic, prophylactic, in-vivo, or diagnostic capacity. By purchasing a product from AAA Biotech, you are explicitly certifying that said products will be properly tested and used in line with industry standard. AAA Biotech and its authorized distribution partners reserve the right to refuse to fulfill any order if we have any indication that a purchaser may be intending to use a product outside of our accepted criteria.Disclaimer
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