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:

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

Biological Processes:

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