LKB1 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, thus promoting 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, PTEN and possibly 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 center in response to DNA damage. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton. Required for cortical neuron 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 of p53/TP53-dependent apoptosis via interaction with p53/TP53: translocates to the mitochondrion during apoptosis and regulates p53/TP53-dependent apoptosis pathways. In vein endothelial cells, inhibits PI3K/Akt signaling activity and thus induces apoptosis in response to the oxidant peroxynitrite (in vitro). Regulates UV radiation-induced DNA damage response mediated by CDKN1A. In association with NUAK1, phosphorylates CDKN1A in response to UV radiation and contributes to its degradation which is necessary for optimal DNA repair. Isoform 2: Has a role in spermiogenesis. Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. LKB1 subfamily. Ubiquitously expressed. Strongest expression in testis and fetal liver. 2 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: Autophagy; CAMK group; CAMKL family; EC; Kinase, protein; LKB subfamily; Protein kinase, CAMK; Protein kinase, Ser/Thr (non-receptor); Tumor suppressor
Chromosomal Location of human Ortholog: 19p13.3
Cellular Component:  cytoplasm; cytosol; intracellular protein-containing complex; membrane; mitochondrion; nucleoplasm; nucleus; serine/threonine protein kinase complex; Z disc
Molecular Function:  ATP binding; LRR domain binding; magnesium ion binding; p53 binding; protein binding; protein kinase activator activity; protein serine kinase activity; protein serine/threonine kinase activity; protein-containing complex binding
Biological Process:  activation of protein kinase activity; anoikis; autophagy; axonogenesis; cellular response to UV-B; dendrite extension; DNA damage response; epithelial cell proliferation involved in prostate gland development; establishment of cell polarity; G1 to G0 transition; glucose homeostasis; Golgi localization; intrinsic apoptotic signaling pathway by p53 class mediator; negative regulation of canonical Wnt signaling pathway; negative regulation of cell growth; negative regulation of cell population proliferation; negative regulation of cold-induced thermogenesis; negative regulation of epithelial cell proliferation involved in prostate gland development; negative regulation of TORC1 signaling; peptidyl-threonine phosphorylation; positive regulation of autophagy; positive regulation of axonogenesis; positive regulation of gluconeogenesis; positive regulation of protein localization to nucleus; positive regulation of transforming growth factor beta receptor signaling pathway; positive regulation of vesicle transport along microtubule; positive thymic T cell selection; protein autophosphorylation; protein dephosphorylation; protein localization to nucleus; protein phosphorylation; regulation of cell cycle; regulation of cell growth; regulation of dendrite morphogenesis; regulation of protein kinase B signaling; regulation of signal transduction by p53 class mediator; regulation of Wnt signaling pathway; response to activity; response to glucagon; response to ionizing radiation; response to lipid; response to thyroid hormone; signal transduction; spermatogenesis; T cell receptor signaling pathway; tissue homeostasis; vasculature development
Disease: Melanoma, Cutaneous Malignant, Susceptibility To, 1; Pancreatic Cancer; Peutz-jeghers Syndrome; Testicular Germ Cell Tumor
Reference #:  Q15831 (UniProtKB)
Alt. Names/Synonyms: hLKB1; Liver kinase B1; LKB1; PAR-4; PAR4; PJS; polarization-related protein LKB1; Renal carcinoma antigen NY-REN-19; serine/threonine kinase 11; Serine/threonine-protein kinase 11; Serine/threonine-protein kinase LKB1; Serine/threonine-protein kinase STK11; STK11
Gene Symbols: STK11
Molecular weight: 48,636 Da
Basal Isoelectric point: 7.12  Predict pI for various phosphorylation states
CST Pathways:  AMPK Signaling  |  Insulin Receptor Signaling  |  mTOR Signaling  |  Translation: eIF4E and p70S6K  |  Warburg Effect
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
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Cross-references to other databases:  AlphaFold  |  STRING  |  cBioPortal  |  Wikipedia  |  Reactome  |  neXtProt  |  Protein Atlas  |  BioGPS  |  KinBase  |  Pfam  |  RCSB PDB  |  ENZYME  |  Phospho3D  |  Phospho.ELM  |  NetworKIN  |  GeneCards  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene  |  InnateDB  |  Ensembl Protein