breast cancer Inherited changes in the STK11 gene greatly increase the risk of developing breast cancer, as well as other types of cancer, as part of Peutz-Jeghers syndrome (described above). These mutations are thought to account for only a small fraction of all breast cancer cases. ovarian cancer Genetics Home Reference provides information about ovarian cancer. Peutz-Jeghers syndrome Inherited mutations in the STK11 gene cause Peutz-Jeghers syndrome, a condition characterized by the development of noncancerous growths called hamartomatous polyps in the gastrointestinal tract and a greatly increased risk of developing several types of cancer. More than 340 STK11 gene mutations have been identified in people with this condition. Many of these mutations result in the production of an abnormally short, nonfunctional version of the serine/threonine kinase 11 enzyme. Other mutations change single protein building blocks (amino acids) used to build the enzyme. Mutations in the STK11 gene impair the enzyme's tumor suppressor function, allowing cells to grow and divide without control or order. This uncontrolled cell growth can lead to the formation of hamartomatous polyps and cancerous tumors. other cancers Noninherited (somatic) mutations in the STK11 gene have been found in various forms of cancer. Somatic mutations are acquired during a person's lifetime and are present only in certain cells. They do not occur as part of a cancer syndrome. Somatic STK11 gene mutations have been identified in a form of lung cancer called non-small cell lung carcinoma, cervical cancer, colorectal cancer, an aggressive type of skin cancer called melanoma, and pancreatic cancer. These mutations impair the function of serine/threonine kinase 11, which can allow cells to grow and divide uncontrollably and contribute to the formation of a cancerous tumor.

     The STK11 gene (also called LKB1) provides instructions for making an enzyme called serine/threonine kinase 11. This enzyme is a tumor suppressor, which means that it helps keep cells from growing and dividing too fast or in an uncontrolled way. This enzyme helps certain types of cells correctly orient themselves within tissues (polarization) and assists in determining the amount of energy a cell uses. This kinase also promotes a type of programmed cell death known as apoptosis. In addition to its role as a tumor suppressor, serine/threonine kinase 11 function appears to be required for normal development before birth.

The following transcription factors affect gene expression:

• p53
• CREB
• deltaCREB
• STAT3
• HNF-4alpha1
• HNF-4alpha2
• NF-1

Tissue specificity:

Ubiquitously expressed. Strongest expression in testis and fetal liver.

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.

Molecular Function:

• Magnesium Ion Binding
• P53 Binding
• Protein Serine/Threonine Kinase Activity
• Atp Binding

Biological Processes:

• Regulation Of Cell Growth
• Tissue Homeostasis
• Vasculature Development
• Protein Phosphorylation
• Autophagy
• Cellular Response To Dna Damage Stimulus
• Cell Cycle Arrest
• Spermatogenesis
• Spermatid Development
• Axonogenesis
• Negative Regulation Of Cell Proliferation
• Response To Ionizing Radiation
• Positive Regulation Of Autophagy
• Establishment Of Cell Polarity
• Regulation Of Wnt Signaling Pathway
• Negative Regulation Of Cell Growth
• Positive Regulation Of Transforming Growth Factor Beta Receptor Signaling Pathway
• Activation Of Protein Kinase Activity
• Tcr Signalosome Assembly
• Glucose Homeostasis
• Anoikis
• Positive Thymic T Cell Selection
• Protein Autophosphorylation
• Regulation Of Dendrite Morphogenesis
• Positive Regulation Of Peptidyl-Tyrosine Phosphorylation
• Positive Regulation Of Axonogenesis
• T Cell Receptor Signaling Pathway
• Negative Regulation Of Lipid Biosynthetic Process
• Golgi Localization
• Regulation Of Protein Kinase B Signaling
• Canonical Wnt Signaling Pathway
• Negative Regulation Of Epithelial Cell Proliferation Involved In Prostate Gland Development
• Cellular Response To Uv-B
• Positive Regulation Of Protein Serine/Threonine Kinase Activity
• Intrinsic Apoptotic Signaling Pathway By P53 Class Mediator
• Dendrite Extension
• Positive Regulation Of Protein Localization To Nucleus
• Regulation Of Signal Transduction By P53 Class Mediator
• Negative Regulation Of Torc1 Signaling