Ribosomal protein S6 (rpS6 or eS6) is a component of the 40S ribosomal subunit and is therefore involved in translation. Mouse model studies have shown that phosphorylation of eS6 is involved in the regulation of cell size, cell proliferation, and glucose homeostasis. [5] [6] [7]
Studies show that the p70 ribosomal protein S6 kinases (S6K1 and S6K2) and p90 ribosomal protein S6 kinases (RSK) both phosphorylate eS6 and that S6K1 and S6K2 predominate this function.
Pathways leading to the induction of human eS6 phosphorylation have been found to enhance IL-8 protein synthesis. This mechanism is dependent on A/U-rich proximal sequences (APS) found in the 3'UTR of IL-8 immediately after the stop codon. [8]
The insulin receptor (IR) is a transmembrane receptor that is activated by insulin, IGF-I, IGF-II and belongs to the large class of receptor tyrosine kinase. Metabolically, the insulin receptor plays a key role in the regulation of glucose homeostasis, a functional process that under degenerate conditions may result in a range of clinical manifestations including diabetes and cancer. Insulin signalling controls access to blood glucose in body cells. When insulin falls, especially in those with high insulin sensitivity, body cells begin only to have access to lipids that do not require transport across the membrane. So, in this way, insulin is the key regulator of fat metabolism as well. Biochemically, the insulin receptor is encoded by a single gene INSR, from which alternate splicing during transcription results in either IR-A or IR-B isoforms. Downstream post-translational events of either isoform result in the formation of a proteolytically cleaved α and β subunit, which upon combination are ultimately capable of homo or hetero-dimerisation to produce the ≈320 kDa disulfide-linked transmembrane insulin receptor.
Glycogen synthase is a key enzyme in glycogenesis, the conversion of glucose into glycogen. It is a glycosyltransferase that catalyses the reaction of UDP-glucose and n to yield UDP and n+1.
Interleukin 8 is a chemokine produced by macrophages and other cell types such as epithelial cells, airway smooth muscle cells and endothelial cells. Endothelial cells store IL-8 in their storage vesicles, the Weibel-Palade bodies. In humans, the interleukin-8 protein is encoded by the CXCL8 gene. IL-8 is initially produced as a precursor peptide of 99 amino acids which then undergoes cleavage to create several active IL-8 isoforms. In culture, a 72 amino acid peptide is the major form secreted by macrophages.
Mitogen-activated protein kinase 3, also known as p44MAPK and ERK1, is an enzyme that in humans is encoded by the MAPK3 gene.
DNA-dependent protein kinase, catalytic subunit, also known as DNA-PKcs, is an enzyme that in humans is encoded by the gene designated as PRKDC or XRCC7. DNA-PKcs belongs to the phosphatidylinositol 3-kinase-related kinase protein family. The DNA-Pkcs protein is a serine/threonine protein kinase comprising a single polypeptide chain of 4,128 amino acids.
Activating transcription factor 6, also known as ATF6, is a protein that, in humans, is encoded by the ATF6 gene and is involved in the unfolded protein response.
Ribosomal protein S6 kinase alpha-1 is an enzyme that in humans is encoded by the RPS6KA1 gene.
Ribosomal protein S6 kinase beta-1 (S6K1), also known as p70S6 kinase, is an enzyme that in humans is encoded by the RPS6KB1 gene. It is a serine/threonine kinase that acts downstream of PIP3 and phosphoinositide-dependent kinase-1 in the PI3 kinase pathway. As the name suggests, its target substrate is the S6 ribosomal protein. Phosphorylation of S6 induces protein synthesis at the ribosome.
DNA damage-inducible transcript 3, also known as C/EBP homologous protein (CHOP), is a pro-apoptotic transcription factor that is encoded by the DDIT3 gene. It is a member of the CCAAT/enhancer-binding protein (C/EBP) family of DNA-binding transcription factors. The protein functions as a dominant-negative inhibitor by forming heterodimers with other C/EBP members, preventing their DNA binding activity. The protein is implicated in adipogenesis and erythropoiesis and has an important role in the cell's stress response.
Eukaryotic translation initiation factor 2 subunit 1 (eIF2α) is a protein that in humans is encoded by the EIF2S1 gene.
5'-AMP-activated protein kinase catalytic subunit alpha-1 is an enzyme that in humans is encoded by the PRKAA1 gene.
Dual specificity tyrosine-phosphorylation-regulated kinase 1A is an enzyme that in humans is encoded by the DYRK1A gene. Alternative splicing of this gene generates several transcript variants differing from each other either in the 5' UTR or in the 3' coding region. These variants encode at least five different isoforms.
Ribosomal protein S6 kinase alpha-5 is an enzyme that in humans is encoded by the RPS6KA5 gene. This kinase, together with RPS6KA4, are thought to mediate the phosphorylation of histone H3, linked to the expression of immediate early genes.
Ribosomal protein S6 kinase alpha-2 is an enzyme that in humans is encoded by the RPS6KA2 gene.
Ribosomal protein S6 kinase beta-2 is an enzyme that in humans is encoded by the RPS6KB2 gene.
Eukaryotic elongation factor-2 kinase, also known as calmodulin-dependent protein kinase III (CAMKIII) and calcium/calmodulin-dependent eukaryotic elongation factor 2 kinase, is an enzyme that in humans is encoded by the EEF2K gene.
Death-associated protein kinase 3 is an enzyme that in humans is encoded by the DAPK3 gene.
Ribosomal protein S6 kinase alpha-4 is an enzyme that in humans is encoded by the RPS6KA4 gene.
Carbohydrate-responsive element-binding protein (ChREBP) also known as MLX-interacting protein-like (MLXIPL) is a protein that in humans is encoded by the MLXIPL gene. The protein name derives from the protein's interaction with carbohydrate response element sequences of DNA.
Glucose-6-phosphate exchanger SLC37A1 is a protein that in humans is encoded by the SLC37A1 gene. SLC37A1 locates to the membrane of the endoplasmic reticulum (ER), and is a glucose 6-phosphate:inorganic phosphate antiporter, transporting glucose 6-phosphate from the cytoplasm into the lumen of the ER, while transporting phosphate in the opposite direction.