Sandbox 465: Difference between revisions

STK11 has a molecular mass of approximately 50kDa and is the catalytically active unit of a heterotrimeric complex with STE20-related adaptor (STRAD) and mouse protein 25 (MO25). STRAD, a pseudokinase, induces a conformational change in STK11 to form the catalytically active state which transports STK11 from the nucleus to the cytoplasm. MO25, a scaffold protein, strengthens the interaction between STK11 and STRAD, and as a result enhances the kinase activity of STK11. <ref name="STK11" />STK11 has a ATP binding site located at Lys78, a basic amino acid, and a nucleotide binding site (9 residues) consisting of hydrophobic amino acids (such as Gly, Leu, and Val), hydrophilic amino acids (such as Ser and Tyr), a basic amino acid (Lys), and an acidic amino acid (Glu). STK11 also has an active site at Asp176, which serves as a proton acceptor. <ref name="LKB1" />

The STK11 gene is located on chromosome 19 on the p arm of the chromosome, also known as the short arm. The exact location is between base pair 1,205,799 and 1,228,435. Location is found in both the nucleus and the cytoplasm. In humans, when STK11 is overexpressed it is mostly located in the nucleus, having limited amounts in the cytoplasm. When a cell is undergoing apoptosis, STK11 translocates into the mitochondria. STK11 is mostly expressed in the seminiferous tubules of the testes, showing higher expression in the fetal tissues than in adult tissues. <ref name ="Nature" />

Serine/Threonine-protein kinase (STK11) is a tumor suppressor that plays a role in cell metabolism, cell polarity, apoptosis and DNA damage response. STK11 controls the activity of the AMP-activated protein kinase (AMPK) family members as well as other non AMPK family members. This enzyme acts by phosphorylating the T-loop within AMPK and non AMPK members. The non AMPK family proteins that it phosphorylates are STRADA, PTEN and possibly p53/TP53. The AMPK family members it phosphorylates are PRKAA1, PRKAA2, BRSK1, BRSK2, MARK1, MARK2 and others but not MELK. STK11 acts as an upstream regulator by mediating phosphorylation and activation of the AMPK catalytic subunits PRKAA1 and PRKAA2. It also regulates activation of autophagy when cells undergo nutrient deprivation, B-cell differentiation in the germinal center in response to DNA damage and inhibition of signaling pathway that promotes cell growth and proliferation when energy levels are low. Its inhibition of PI3K/Akt signaling activity in vein endothelial cells induces apoptosis in response to the oxidant peroxynitrite (in vitro). This enzyme also regulates UV-radiation induced DNA damage response and cell polarity by remodeling the actin cytoskeleton. <ref name="Uniprot" />.