TOR (Target of Rapamycin) is a PIKK (Phosphatidylinositol Kinase-related protein Kinase) that controls cell growth and proliferation. In all eukaryotic cells expressing the protein, TOR function is controlled by nutrient availability, which ensures that protein synthesis is repressed when the supply of precursor amino acids is insufficient. In mammalian cells, one branch of this pathway controls general translational initiation, whereas a separate branch specifically regulates the translation of r-protein (ribosomal protein) mRNAs. In simple organisms, nutrient availability appears to be the major factor influencing TOR activity. In budding yeast, Saccharomyces cerevisiae the TOR pathway similarly regulates general translational initiation, but its specific role in the[..]

The MAPK (Mitogen-Activated Protein Kinase) pathways are highly conserved signaling cascades that convert extracellular signals into various outputs. Each pathway is composed of three classes of protein kinase: MAPK, MAPKK (MAPK Kinase) and MAPKKK (MAPK Kinase Kinase). MAPK is activated by phosphorylation of specific tyrosine and threonine residues by a family of dual-specificity protein kinase MAPKKs. MAPKK is in turn activated by phosphorylation of serine and serine/threonine residues by a family of upstream MAPKKKs. Each of these upstream components plays a role in multiple cell signaling processes. The ERKs (Extracellular-signal Regulated Kinases), SAPK/JNKs (Stress-Activated Protein Kinases/c-Jun N-terminal Kinases), and p38 are the three best characterized[..]

GHRH (Growth Hormone-Releasing Hormone) is a hypothalamic hormone that is essential for normal expansion of the somatotrope lineage during pituitary development. GHRH is produced by GHRH cells in the hypothalamus and reaches the adenohypophysis via the portal system. It stimulates the release of GH (Growth Hormone)/Somatotropin from the adenohypophysis. GH is required for normal postnatal growth, having a critical role in bone growth as well as important regulatory effects on protein, carbohydrate, and lipid metabolism (Ref.1 & 2).GHRH first appears in the human hypothalamus between 18 and 29 weeks of gestation, which corresponds to the appearance of fetal pituitary somatrotropes. It is a 44-amino acid peptide, synthesized by neurons in the hypothalamic arcuate nucleus[..]

Relaxin is a polypeptide hormone that is secreted by the corpus luteum, into the circulation during the menstrual cycle and throughout pregnancy. During the cycle, it stimulates blood vessel growth in the endometrial lining of the uterus during the midluteal phase; coincident with the temporal window during which embryonic implantation occurs. If conception occurs, Relaxin levels rise and remain relatively constant during the entire gestational period (Ref.1). Relaxin is best known for its connective tissue remodeling effects on the female reproductive system. It has diverse actions in the reproductive tract and other tissues during pregnancy. These actions include promotion of growth and dilation of the cervix, growth and quiescence of the uterus, growth and[..]

Normal mammalian sexual maturation and reproductive functions require the integration and precise coordination of hormones at the hypothalamic, pituitary, and gonadal levels. The hypothalamic GnRH (Gonadotropin Releasing Hormone), also called LHRH (Luteinizing Hormone Releasing Hormone), is a key regulator in this system (the hypothalamic-pituitary-gonadal axis), that plays a decisive role in the neuroendocrine regulation of human reproduction. GnRH is a decapeptide, released in an episodic manner from the hypothalamic GnRH neurons. The pulsatile delivery of GnRH to the anterior pituitary gland is essential to maintain the circulating gonadotropin profiles. It acts via a specific GPCR (G-Protein Coupled Receptor): GnRHR (GnRH Receptor) and triggers the synthesis of[..]

MAPK (Mitogen-Activated Protein Kinase) signal transduction pathways are evolutionarily conserved in eukaryotic cells and transduce signals in response to a variety of extracellular stimuli. Each pathway is composed of three classes of protein kinase: MAPK, MAPKK (MAPK Kinase) and MAPKKK (MAPK Kinase Kinase). MAPK is activated by tyrosine and threonine phosphorylation catalyzed by a family of dual-specificity protein kinase MAPKKs. MAPKK is in turn activated by phosphorylation mediated by MAPKKK. Cascades of MAPKs mediate responses such as cell proliferation, differentiation, and the regulation of metabolic pathways. There are multiple MAPKs in eukaryotes. Three subgroups of the MAPK superfamily have been identified in mammals: ERK (Extracellular signal-Regulated[..]

Listeria monocytogenes is a potentially deadly food-borne pathogen that colonizes the gastrointestinal tract of several mammalian species, and can also cause invasive disease and systemic spread if it crosses the intestinal epithelial barrier. Listeria monocytogenes  evolved two major molecular invasion proteins, referred to here as invasins: Internalin A (InlA, Internalin) and Internalin B (InlB). These proteins promote internalization into nonphagocytic cells where Listeria monocytogenes  can grow in the cytosol as a facultative intracellular pathogen and directly spread to neighboring cells through actin-based motility. InlA-mediated entry is restricted to a few epithelial cells, whereas, InlB promotes entry into various cell types, such as hepatocytes,[..]

Erythropoiesis is a major pathway for Erythrocyte production, by which pluripotent Hematopoietic Stem Cells give rise to mature end stage cells via a series of differentiations. Epo (Erythropoietin), a glycoprotein hormone and a multifunctional Hematopoietic Cytokine ligand, is the master regulator of Erythropoiesis. As a major function, it monitors the safe passage of the committed Erythroid progenitor cells through several physiological and developmental stages by stimulating Growth, preventing Apoptosis, and promoting terminal differentiation. In addition to its immense survival strategies, Epo initiates Hemoglobin synthesis and is an essential viability and Growth factor in the maintenance of a steady physiological level of circulating Erythrocyte mass which[..]

Programmed cell death, a form of altruistic suicide is a genetically controlled means of cellular self-destruction that leads to dismantling and packaging of cell material for removal by phagocytosis. All cells possess the ability to undergo programmed cell death (otherwise known as apoptosis), and the process is essential for normal development to shape organs and tissues as well as to remove damaged cells. Although the cell may require de novo synthesis of some signaling molecules, the machinery for apoptosis is constantly present and may be rapidly activated. Therefore, the process of apoptosis needs tight regulation, and such regulation has been shown to be brought about by signaling through peptide growth factors including the IGF (Insulin-Like Growth Factor)[..]

Immune and inflammatory responses are rightly regulated to maintain a homoeostatic balance between an effective immune response and tissue damage to the host. Nitric Oxide is the principal mediator of many of the cytokine-inducible macrophage activities during a normal cell-mediated immune response. STK (Stem Cell-Derived Tyrosine Kinase), the murine homolog of the human RON (RON Protein Tyrosine Kinase/ Receptor d’origine nantais), is expressed on murine resident peritoneal macrophages. The ligand for STK, MSP (Macrophage Stimulating Protein), is a serum protein that is activated by members of the Coagulation Cascade (Tissue Clotting Factors) in response to tissue damage. MSP has an inhibitory effect on the production of Nitric Oxide by activated peritoneal[..]

MSP (Macrophage-Stimulating Protein) also known as HGFL (Hepatocyte Growth Factor–Like Protein,) is a plasminogen-like growth factor that mediates its biological activities by activating the receptor tyrosine kinase RON  also known as MSTR1, (Macrophage Stimulating Receptor-1), a member of the MET proto-oncogene family . The alpha-chain of MSP consists of an N-terminal PAN module followed by four kringle domains and is disulfide linked to the trypsin-like beta-chain. This protein is secreted as an inactive single-chain precursor pro-MSP, which requires proteolytic cleavage at the Ser-Lys-Leu-Arg483, Val484 bond to attain functional activity. MSP is constitutively expressed by hepatic parenchymal cells, as well as in lungs, adrenal glands, placenta,[..]

Cholesterol is the common precursor of all steroid hormones and is biosynthesized in many tissues. Steroid hormones are characterized by a common basic structure of cyclopentane-perhydro-phenantrene, a polycyclic complex of 17 carbon atoms forming a four-ring system. Altering a side chain or subsistent group of a cholesterol molecule produces various steroids molecules.  Pregnenolone and progesterone are molecules derived from cholesterol (Ref.1&2).Cholesterol is converted to pregnenolone inside the mitochondria by the enzyme CYP11A1 (cytochrome P450 family 11 subfamily A member 1). This conversion is the first step in the synthesis of steroids and is termed as the cholesterol side-chain cleavage reaction. Pregnenolone then passes through the mitochondrial[..]