QIAGEN Website    Quick Order    Online Seminar    Contact    My Account
Home  >  Resources  >  Pathway Central

Pathway Central

Powered by Protein Lounge

Toxicology and Drug Metabolism related Pathways

Activation of cAMP-Dependent PKA [ Details | Top ]
cAMP (Cyclic Adenosine 3',5'-monophosphate) is the first identified second messenger, which has a fundamental role in the cellular response to many extracellular stimuli. The cAMP signaling pathway controls a diverse range of cellular processes. Indeed, not only did cAMP provide the paradigm for the second messenger concept, but also provided the paradigm for signaling compartmentalization. The different receptors, chiefly the GPCRs (G-Protein Coupled Receptors), Alpha and Beta-ADRs (Adrenergic Receptors), Growth Factor receptors, CRHR (Corticotropin Releasing Hormone Receptor), GcgR (Glucagon Receptor) ...

AHR Pathway - New [ Details | Top ]
AHR (Aryl Hydrocarbon Receptor) is a member of the bHLH (basic Helix-Loop-Helix)- PAS (Per-ARNT-Sim) family of transcriptional regulators that control a variety of developmental and physiological events, including Neurogenesis, Tracheal and Salivary duct formation, Toxin metabolism, Circadian rhythms, response to Hypoxia and Hormone Receptor function. The unique feature of all bHLH-PAS proteins is the PAS domain, named after the first three proteins identified with this motif, the Drosophila Per, Human ARNT and Drosophila Sim. The PAS domain consists of 260310 amino acids and incorporates two well-conserved hydrophobic re...

All-trans-retinoic acid signaling [ Details | Top ]
Retinoic Acid, a lipophilic molecule and a metabolite of Vitamin-A (all-trans-Retinol), affects gene transcription and modulates a wide variety of biological processes like Cell Proliferation, Differentiation, including Apoptosis. Retinoic Acid mediated gene transcription depends on the rate of transport of Retinoic Acid to target cells and the timing of exposure of Retinoic Acid to RARs (Retinoic Acid Receptors) in the target tissues. The all-trans-Retinoic Acid, the Carboxylic Acid form of Vitamin-A is of biological significance since it has high circulating levels than other isomers of Retinoic Acid. The targets of all-trans-Retinoic Acid and RARs include a multitude...

cAMP Pathway [ Details | Top ]
cAMP (Cyclic Adenosine 3',5'-monophosphate) is the first identified second messenger, which has a fundamental role in the cellular response to many extracellular stimuli. The cAMP signaling pathway controls a diverse range of cellular processes. Indeed, not only did cAMP provide the paradigm for the second messenger concept, but also provided the paradigm for signaling compartmentalization. The different receptors, chiefly the GPCRs (G-Protein Coupled Receptors), Alpha and Beta-ADRs (Adrenergic Receptors), Growth Factor receptors, CRHR (Corticotropin Releasing Hormone Receptor), GcgR (Glucagon Receptor), DCC...

Caspase Cascade [ Details | Top ]
Caspases are a family of cysteine proteases that act in concert in a cascade triggered by apoptosis signaling. The culmination of this cascade is the cleavage of a number of proteins in the cell, followed by cell disassembly, cell death, and, ultimately, the phagocytosis and removal of the cell debris. The Caspase cascade is activated by two distinct routes: one from cell surface and the other from mitochondria (Ref.1). The pathway leading to Caspase activation varies according to the apoptotic stimulus. Initiator Caspases (including 8, 9, 10 and 12) are closely coupled to pro-apototic signals. Pro-apoptotic stimuli include the FasL (Fas Ligand), TNF...

DNA Repair Mechanisms [ Details | Top ]
Cells are constantly under threat from the cytotoxic and mutagenic effects of DNA damaging agents. Environmental DNA-damaging agents include UV light and ionizing radiation, as well as a variety of chemicals encountered in foodstuffs, or as air- and water-borne agents. Endogenous damaging agents include metabolites that can act as alkylating agents and the ROS (Reactive Oxygen Species) that arise during respiration. DNA repair enzymes continuously monitor chromosomes to correct damaged nucleotide residues generated by these exogenous and endogenous agents and exposure to carcinogens and cytotoxic compounds...

eNOS Signaling - New [ Details | Top ]
NO (Nitric Oxide) is a short-lived free radical gas involved in diverse physiological and pathological processes. It is produced along with L-Citrulline by the oxidation of L-Arginine and catalyzed by three different isoforms of NOS (NO Synthase). Type-I nNOS (neuronal NOS) and Type-III eNOS (endothelial NOS) are constitutively expressed as latent enzymes and require a higher concentration of Ca2+ for the enzyme activity. In contrast, Type-II iNOS (inducible NOS) is Ca2+ independent because its high affinity for Ca2+/Calm (Calmodulin) renders the enzyme active even at basal levels of intracellular Ca2+ (Ref.1 & 2). The ca...

ERK Signaling [ Details | Top ]
The MAPK (Mitogen-Activated Protein Kinase) pathway is one of the primordial signaling systems that nature has used in several permutations to accomplish an amazing variety of tasks. It exists in all eukaryotes, and controls such fundamental cellular processes as Proliferation, Differentiation, Survival and Apoptosis. Mammalian MAPK can be divided into four groups based on their structure and function: ERKs (Extracellular signal-Regulated Kinases), p38MAPKs, JNKs (c-Jun NH2-terminal Kinases) and ERK5 (Extracellular signal-Regulated Kinase-5) or BMK. Activation of these MAPKs occurs through a cascade of upstream kinases...

Fas Signaling [ Details | Top ]
Fas (also called Apo1 or CD95) is a death domain-containing member of the TNFR (Tumor Necrosis Factor Receptor) superfamily. It has a central role in the physiological regulation of Programmed Cell Death and has been implicated in the pathogenesis of various malignancies and diseases of the immune system. Although the FasL (Fas Ligand)-Fas system has been appreciated mainly with respect to its death-inducing function, it also transduces proliferative and activating signals through pathways that are still poorly defined. The Fas Receptor induces an apoptotic signal by binding to....

iNOS Signaling - New [ Details | Top ]
Microorganisms have developed several mechanisms to survive in their hosts' environments. These include competition with their hosts for metal acquisition and resistance to host defenses such as NO (Nitric Oxide), a cytotoxic weapon generated by macrophages. In eukaryotic cells, NO is metabolically produced by NOS (NO Synthase) from L-Arginine, O2 (Molecular Oxygen), and NADPH (Nicotinamide Adenine Dinucleotide, Reduced). In macrophages, an inducible NO synthase (iNOS or NOS2) is produced after activation by endotoxins or cytokines and generates copious amounts of NO presumably to help kill or inhibit the growth of invadin...

IP3 Pathway [ Details | Top ]
IP3 (Inositol 1,4,5-triphosphate), also known as a second messenger, is a molecule that functions to transfer a chemical signal received by the cell, such as from a hormone, neurotransmitters, growth factors and hypertrophic stimuli such as AngII (Angiotensin-II), Beta-adrenergic receptor agonists, and ET1 (Endothelin-1) to various signaling networks within the cell. IP3 is known to play a crucial role in initiating and propagating these messages; however, the precise mechanism of how IP3 relates to the next element in its signaling pathway, the calcium wave, remains highly controversial. The receptors for IP3, IP3R (IP3 Receptor) constitute a family...

JNK Pathway [ Details | Top ]
MAPKs (Mitogen-Activated Protein Kinases) are Serine-threonine protein Kinases that are activated in response to a variety of extracellular stimuli and mediate signal transduction from the cell surface to the nucleus. MAPKs are expressed in multiple cell types including Cardiomyocytes, Vascular Endothelial cells, and Vascular Smooth Muscle Cells. Three major MAPKs include ERKs (Extracellular signal-Regulated Kinases), JNKs (c-Jun NH(2)-terminal protein Kinases), and p38 Kinases. Members of the JNK/SAPK (Stress-Activated Protein Kinase) family of MAPKs are strongly stimulated by numerous Environmental Stresses...

MAPK family pathway [ Details | Top ]
Protein kinases are ubiquitous enzymes that are able to modulate the activities of other proteins by adding phosphate groups to their tyrosine, serine, or threonine amino acids (phosphorylation). MAPKs (Mitogen-Activated Protein Kinases), which are activated by many different signals, belong to a large family of serine/threonine protein kinases that are conserved in organisms as diverse as yeast and humans. MAPKs deliver extracellular signals from activated receptors to various cellular compartments, notably the nucleus, where they direct the execution of appropriate genetic programs, including activation of gene transcription...

MAPK Signaling [ Details | Top ]
Intracellular signaling cascades are the main routes of communication between the Plasma membrane and regulatory targets in various intracellular compartments. Sequential activation of Kinases is a common mechanism of signal transduction in many cellular processes. During the past decade, several related intracellular signaling cascades have been elucidated, which are collectively known as MAPK (Mitogen-Activated Protein Kinase) signaling cascades. The MAPKs are a group of protein Serine/threonine Kinases that are activated in response to a variety of extracellular stimuli and mediate ....

Mismatch Repair - New [ Details | Top ]
In all organisms, DNA repair processes are crucial to maintain the integrity of the genome through the generations. Many animals minimize the number of cell divisions and thus the chance to accumulate mutations from one to the next generation. The DNA MMR (Mismatch Repair) apparatus has an important function in stabilizing the genome, and the protein components of this system are highly conserved in all pro- and eukaryotic systems. The MMR system is responsible for the post-replicative repair of mismatches and small single stranded DNA loops, and it is critically involved in preventing recombination between homologous DNA...

Mitochondrial Apoptosis - New [ Details | Top ]
Apoptosis is a naturally occurring process by which a cell is directed to Programmed Cell Death. Apoptosis is based on a genetic program that is an indispensable part of the development and function of an organism. In this process, cells that are no longer needed or that will be detrimental to an organism or tissue are disposed of in a neat and orderly manner; this prevents the development of an inflammatory response, which is often associated with Necrotic cell death. There are at least two broad pathways that lead to Apoptosis, an 'Extrinsic' and an 'Intrinsic' Pathway. In both pathways, signaling results in the activati...

mTOR Pathway [ Details | Top ]
mTOR (Mammalian Target of Rapamycin) is a 289-kDa serine/threonine protein kinase and a member of the PIKK (Phosphatidylinositol 3-Kinase-related Kinase) family. The protein consists of a Catalytic Kinase domain, an FRB (FKBP12–Rapamycin Binding) domain, a putative Auto-inhibitory domain (Repressor domain) near the C-terminus and up to 20 tandemly repeated HEAT motifs at the Amino terminus, as well as FAT (FRAP-ATM-TRRAP) and FATC (FAT C-terminus) domains. The C-terminus of TOR is highly homologous to the catalytic domain of PI3K (Phosphatidylinositol 3-Kinase). TOR proteins are evolutionarily conserved from yeast...

P38 Signaling - New [ Details | Top ]
Cellular responses to many external stimuli involve the activation of several types of MAPK (Mitogen-Activated Protein Kinase) signaling pathways. MAPKs are a family of Serine/threonine kinases that comprise 3 major subgroups, namely, ERK (Extracellular signal-Regulated Kinase), p38 MAPK and JNK (c-Jun N-terminal Kinases). Despite the diversity in function and upstream signaling events, MAPKs are always activated by a highly conserved mechanism that involves phosphorylation on both a Thr (Threonine) and a Tyr (Tyrosine) residue catalyzed by a MAPK kinase. The phosphorylation motif Thr-Xaa-Tyr is located in the so called ac...

PAK Pathway - New [ Details | Top ]
PAKs (p21-Activated Protein Kinases) are a growing family of serine/threonine protein kinases, which are activated in response to extracellular signals and regulate cell shape and motility. PAKs regulate diverse cellular functions, including gene expression, cytoskeletal actin assembly, MAPK (Mitogen-Activated Protein Kinase) pathways, neurite outgrowth, cell cycle control, and cell apoptosis (Ref.1). The mammalian PAK family consists of six members, which can be divided into two subfamilies according to sequence homology. The first subfamily consists of PAK1 (Alpha-PAK), PAK2 (Gamma-PAK, PAK I) and PAK3 (Beta-PAK). PAK1 a...

Ubiquitin-Proteasome Dependent Proteolysis - New [ Details | Top ]
The Proper functioning of a cell requires careful control of the levels of important structural proteins, enzymes, and regulatory proteins. Protein molecules are continuously synthesised and degraded in all living organisms. The concentration of individual cellular proteins is determined by a balance between the rates of synthesis and degradation, which in turn are controlled by a series of regulated biochemical mechanisms. Differences in the rates of protein synthesis and breakdown result in cellular and tissue atrophy (loss of proteins from cells) and hypertrophy (increase in protein content of cells). Precise control of...