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)[..]

The Eph family forms the largest group of RTKs (Receptor Tyrosine Kinases) comprising 14 members in mammals that play critical roles in diverse biological processes during development as well as in the mature animal. They are activated by membrane-bound ligands called Ephrins, which are classified into two subclasses based on their mode of membrane anchorage. The Ephrin-A ligands are GPI (Glycosylphosphatidylinositol)-linked and prefer to bind to EphA Receptors. The Ephrin-B ligands (Ephrin-B1–B3), which possess a transmembrane moiety and a short cytoplasmic domain, bind to EphB Receptors (EphB1–B6). The interactions between Ephrins and Eph Receptors are generally promiscuous within each subclass (Ref.1). Upon stimulation by Ephrin ligands, Eph Receptors[..]

In organisms as diverse as fruit flies and mammals, circadian rhythms are controlled by a transcriptional feedback system whose activity fluctuates as a function of the light-dark cycle. In mammals, the master clock (circadian pacemaker) resides in the SCN (Suprachiasmatic Nucleus) of the brain's hypothalamus and this endogenous clock drives physiology and behavior. In the absence of external time cues, the SCN master clock generates cycles of approximately but not exactly 24 hours, and its phase must therefore be readjusted every day. This task depends on the retina, which detects changes in light intensity during the day's light-dark cycle (the photoperiod) and transmits this information to the SCN neurons (Ref.1). The mammalian circadian feedback[..]

Estrogens are a class of steroid hormones that play a central role in reproduction, and are regarded as the powerful female hormones that make a girl develop into a woman capable of reproduction. Estrogenic steroids, that include: E1 (Estrone), E2 (Estradiol/17-beta Estradiol) and E3 (Estriol), regulate cellular functions in a wide variety of tissues and influence proliferation in the female reproductive tract and mammary gland. It is this proliferative role of these hormones that, a woman's risk for breast and uterine cancer is often associated with lifetime exposure to estrogen. Estrogens induce proliferation of cancer cells by stimulating G1/S transition and the subsequent progression of cell cycle (Ref.1).In the uterus, estrogen triggers the proliferation of[..]

In numerous processes that are vital for the development and maintenance of organism function, cells must communicate crucial information to respond appropriately to the changing environment. As such, RTKs (Receptor Tyrosine Kinases) are transmembrane proteins, which, on receiving an external stimulus, respond by transmitting a signal to the inside of the cell. Of all the RTKs that are found in the human genome, the Eph Receptor family and their ligands the Ephrins, constitutes the largest family.The Eph family of RTKs which has 14 members and their ligands, the Ephrins, are prominently involved in several developmental processes such as boundary formation, cell migration, axon guidance, synapse formation and angiogenesis. In vertebrates, Eph Receptors are divided into[..]

Interleukin 3 (IL3) is a T cell-derived glycoprotein involved in cell proliferation, survival and differentiation. It regulates haemopoiesis, the formation of blood cells in the body. IL3, also called multi-CSF (multi-lineage colony stimulating factor), is produced by T cells and mast cells, after activation with mitogens or antigens. It was first isolated from murine bone marrow cells and is also believed to be expressed in neurons and astrocytes of the hippocampus, suggesting an important role in central nervous system (Ref.1). It signals through interactions with cell surface receptors.    IL3 receptor (IL3R) is composed of two polypeptide chains, a unique alpha subunit and a common Beta subunit IL3RB (the common beta chain), which is shared by[..]

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that primarily affects the lining of the synovial joints and is associated with progressive disability, premature death, and socioeconomic burdens.It is characterized by chronic inflammation and synovial hyperplasia that eventually lead to cartilage and bone destruction. Synovial fibroblasts are mesenchymal cells recognized as a key cell population in RA due to their hyperproliferative and hypersensitive properties in the inflammatory milieu and hyperproduction of both inflammatory cytokines and matrix-degrading enzymes.Macrophages are major components in the inflammatory cascade and are also important mediators of joint destruction in RA. Large numbers of macrophages are present in synovial tissue and[..]

Small interfering RNAs (siRNAs) are 21–23nt dsRNA (double-stranded RNA) molecules that facilitate potent and sequence-specific gene suppression via the mechanism of RNAi (RNA interference). When introduced into cultured mammalian cells, siRNAs facilitate the degradation of mRNA sequences to which they are homologous, thereby silencing the encoding gene. The basic mechanism behind RNAi is the breaking of a dsRNA matching a specific gene sequence into short pieces of siRNA. These siRNAs with symmetric 2–3nt 3' overhangs and 5'-phosphate and 3'-hydroxyl groups post-transcriptionally silences a gene through mRNA inhibition or degradation. Interference of gene expression by siRNA is now recognized as a naturally occurring biological strategy for[..]

Reelin is a large extracellular glycoprotein involved in the development of architectonic patterns, particularly in the cerebral cortex and hippocampus, where primarily Cajal-Retzius cells synthesize it The Reelin signaling pathway controls neuronal migration and positioning in central nervous system (CNS) development, as well as synaptic plasticity and memory (Ref.1).  Reelin is localized to chromosome 7 in human with serine protease activity containing 3461 amino acids. It contains a signal peptide followed by an N-terminal sequence and a hinge region upstream from eight Reelin repeats of 350–390 amino acids. Each Reelin consists of a signal peptide (S), an F-spondin-like domain (SL), eight consecutive Reelin repeats (R) each harboring an epidermal growth[..]

AKT/PKB Pathway is an evolutionarily conserved serine/threonine kinase Pathway involved in a wide variety of cellular functions, including proliferation, cell survival, differentiation, glucose mobilization, homeostasis, cell migration, and apoptosis. Three isoforms, AKT1,AKT2, and AKT3, are expressed in mammals (Ref.1 & 2). Akt is a central node in cell signaling downstream of growth factors, cytokines, and other cellular stimuli. Aberrant loss or gain of Akt activation underlies the pathophysiological properties of a variety of complex diseases, including type-2 diabetes and cancer (Ref.3). All three isoforms of Akt share a common structure of three domains. The N-terminus of the protein is a PH (Pleckstrin Homology) domain, which interacts with membrane lipid[..]

ATM (Ataxia Telangiectasia Mutated Protein) belongs to a family of Kinases that have sequence homology to PI3K (Phosphoinositide 3-Kinase).ATM is a key regulator of multiple signaling cascades which respond to DNA strand breaks induced by damaging agents IR (Ionizing Radiation), radiometric agents or by normal processes. These responses involve the activation of cell cycle CHK factors (Checkpoints factors), DNA repair and Apoptosis. Its downstream targets include CHK1 (Cell Cycle Checkpoint Kinase-1), CHK2 (Cell Cycle Checkpoint Kinase-2), tumor suppressors like p53 and BRCA (Breast Cancer), DNA repair factors like RAD50, RAD51, GADD45 (Growth Arrest and DNA-Damage-inducible), and other signaling molecules like c-ABL and NF-KappaB (Nuclear Factor-Kappa B) . In[..]

The BCR (B-Cell antigen Receptor) plays a critical role in development, survival, and activation of B cells. The BCR is composed of mIg molecules (Membrane Immunoglobulin) and associated Ig-Alpha/Ig-Beta heterodimer [Ref.1]. The mIg subunits bind antigen and cause receptor aggregation, while the Alpha/Beta subunits transduce signals to the cell interior. Engagement of receptor activates three types of intracellular protein tyrosine kinases, SYK (Spleen Tyrosine Kinase), BTK (Bruton agammaglobulinemia Tyrosine Kinase) and several members of the SRC-family of tyrosine kinases [Ref.2&3]. Once activated, these tyrosine kinases phosphorylate signaling components and thereby activate various signaling pathways, including PIP2 (Phosphatidyl Inositol 4, 5-Bisphosphate)[..]