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PAK Signaling in Fission Yeast
Simple eukaryotes such as yeasts and molds encode multiple PAKs (p21-Activated Kinases) that, like their orthologs in other systems, act downstream of Rho-family GTPases. All PAKs contain an N-terminal PBD (p21 GTPase-Binding-Domain), which confers binding to small GTPases such as CDC42 (Cell Division Cycle-42) or Rac, and a C-terminal protein [...]
Pancreatic Adenocarcinoma
Pancreatic carcinoma is one of the most enigmatic and aggressive malignant diseases. Neoplasms of the pancreas encompass a wide spectrum of benign and malignant tumors. Pancreatic adenocarcinoma, the malignant neoplasm of the exocrine duct cells, accounts for more than ninety percent of all pancreatic tumors (Ref.1). Pancreatic ductal adenocarcinoma evolves [...]
Parkinson’s Disease Pathway
Parkinson's disease is a Neurodegenerative disorder characterized by the progressive loss of Dopaminergic neurons in the substantia nigra and the appearance of intracellular inclusions, named Lewy bodies and Lewy neurites in the remaining nigral neurons. The Substantia nigra is located in the midbrain region of the brain. It consists of [...]
Pathogenesis of ALS
ALS (Amyotrophic Lateral Sclerosis), also known as Lou Gehrig’s disease, is a devastating neurodegenerative disorder, which is characterized by the selective degeneration of upper and lower motor neurons, the large nerve cells connecting the brain to the spinal cord and from the spinal cord to muscles, which control muscle movement. [...]
Pathogenesis of Gliomas
Tumors of the Central Nervous System (CNS) are devastating as they are difficult to treat and may cause grave disability or death. CNS Gliomas pose particularly difficult problems because of their tendency toward malignancy, rate of tumor spread, and the lack of effective therapy. Gliomas are the most common intracranial [...]
Pathogenesis of Helicobacter pylori Infection
The gastrointestinal tract represents an important barrier between human hosts and microbial populations. One potential consequence of host-microbial interactions is the development of mucosal inflammation. A paradigm for such chronic host-microbial relationships is carriage of Helicobacter pylori, Gram-negative bacteria that colonize the stomachs of humans and primates. H. pylori colonization [...]
Pathogenesis of Multiple Sclerosis
MS (Multiple Sclerosis) is an inflammatory and demyelinating disease of the CNS (Central Nervous System). MS is classified according to its clinical course into several categories: benign, RR (Relapsing-Remitting, the most common variant), PR (Progressive-Relapsing), PP (Primary-Progressive) and SP (Secondary-Progressive). MS first manifests itself as a series of attacks followed [...]
Pathogenesis of Rheumatoid Arthritis Recently Updated
RA (Rheumatoid Arthritis) is a chronic debilitating autoimmune disease of unknown etiology affecting diarthrodial joints. Although the disease is characterized by synovitis of the joints, tendon sheaths, and bursae, manifestations that do not involve the synovium are also frequent (Ref.1 & 2). These articular and systemic manifestations are mediated by [...]
Paxillin Interactions
Signals that derive from cell adhesion to the ECM (Extracellular Matrix) regulate important physiological events including cell motility and growth, and most often involve changes in the organization of the actin cytoskeleton. Cells interact with the ECM via transmembrane receptors, termed integrins, located at the cell surface. Binding of integrins [...]
PD-1/PD-L1 Pathway in Cancer
Immune checkpoints refer to a plethora of inhibitory pathways hardwired into the immune system that are crucial for maintaining self-tolerance and limiting collateral tissue damage during anti-microbial immune responses. Checkpoint molecules include Cytotoxic T Lymphocyte Antigen-4 (CTLA-4)
PDGF Pathway
Directed cell migration is a critical feature of several physiological and pathological processes, including development, wound healing, atherosclerosis, immunity, angiogenesis, and metastasis. The migratory response involves actin cytoskeleton reorganization, polarization, cell adhesion and detachment. Thus, migration requires cell communication with adjacent cells and with ECM (Extracellular Matrix Components) and is [...]
PEDF Induced Signaling
Blood vessel growth and stability are under the exquisite control of a network of pro- and anti-angiogenic factors. Disruption of the balance between these factors is a characteristic of tumor growth and many vascular diseases. Endogenous angiogenesis inhibitors, particularly those that act broadly at the earliest stages, are excellent pharmacological [...]
PGC1Alpha Pathway
PGC1Alpha (Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1-Alpha) is a tissue-specific transcriptional coactivator that enhances the activity of many nuclear receptors and coordinates transcriptional programs important for cellular energy metabolism and overall energy homeostasis (Ref.1). It is a key regulator of cardiac mitochondrial functional capacity and participates in the transduction of physiologic [...]
Phagocytosis of Microbes
Phagocytosis, a central component of the innate immune response, is the process whereby specialised cell types recognise and engulf foreign extracellular material. While lower organisms use phagocytosis primarily for the acquisition of nutrients, in higher Eucaryota, the receptors that are able to mediate phagocytosis are expressed almost exclusively in Macrophages, [...]
Phospholipase-C Pathway
Inositol lipid-specific PLC (Phospholipase-C) isozymes are key signaling proteins in the cellular action of many hormones, neurotransmitters, growth factors, and other extracellular stimuli. PLC are soluble proteins that are partly cytosolic and partly associated with membrane. The PLC family in human is comprised of 13 subtypes. On the basis of [...]
PI3K Signaling Recently Updated
The PI3K (Phosphatidylinositde-3-Kinase) family of enzymes regulate diverse biological functions in every cell type by generating lipid second messengers that ultimately results in the mediation of cellular activities such as proliferation, differentiation, chemotaxis, survival, trafficking and Glucose homeostasis. On the basis of structural similarities, the PI3K members are sub-divided into three classes; Class I, II
PI3K Signaling in B-Lymphocyte
PI3Ks (Phosphoinositide-3-Kinases) regulate numerous biological processes, including cell growth, differentiation, survival, proliferation, migration and metabolism. In the immune system, impaired PI3K signaling leads to immunodeficiency, whereas unrestrained PI3K signaling contributes to autoimmunity and Leukemia. The Class I and III PI3Ks basically facilitate B-cell development through defined stages, resulting in at [...]
PI3K Signaling in Caenorhabditis elegans
PI3Ks (Phosphoinositide 3-Kinases) are an important type of lipid kinase that form a large evolutionarily conserved family of enzymes that specifically phosphorylate inositol phospholipids at the D-3 position of the inositol ring. The C. elegans (Caenorhabditis elegans) PI3K is required for functional membrane trafficking machinery (Ref.1). C. elegans PI3K adaptor [...]
PKA Signaling
PKA (Protein Kinase-A) is an enzyme that regulates processes as diverse as growth, development, memory, and metabolism. In its inactivated state, PKA exists as a tetrameric complex of two Catalytic subunits (PKA-C) and a Regulatory (PKA-R) subunit dimer. To date, four regulatory subunits have been identified (RI-Alpha, RI-Beta, RII-Alpha and [...]
PKC-Theta Pathway
An effective immune response depends on the ability of specialized immunocytes to identify foreign molecules and respond by differentiation into mature effector cells. A cell-surface antigen recognition apparatus and a complex intracellular receptor-coupled signal-transducing machinery mediate this tightly regulated process, which operate at high fidelity to discriminate self from nonself [...]
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