Browsing Pathways

The 5-HT4 receptor is primarily found in the CNS, GI tract and PNS. Peripheral receptors have important roles in the function of many organ responses (alimentary tract, urinary bladder, heart and adrenal gland). Alimentary tract receptors have a role in smooth muscle tone, mucosal electrolyte secretion, and the peristaltic reflex. Urinary Bladder receptors control cholinergic/purinergic transmission. Atrial heart receptors produce positive inotropy and tachycardia that can precipitate arrhythmias. This receptor is also thought to have roles in Anxiety, Appetite, GI Motility, Learning, Memory, Mood, and Respiration. The 5-HT4 receptor activates G(s) proteins which lead to the activation of adenylyl cyclase which produces the secondary messenger cAMP. cAMP activates PKA (protein kinase A) which phosphorylates downstream effectors that lead to a specific cellular response.

tut1 tpd52

The mammalian target of rapamycin (mTOR) signaling pathway integrates both intracellular and extracellular signals and serves as a central regulator of cell metabolism, growth, proliferation and survival. Discoveries that have been made over the last decade show that the mTOR pathway is activated during various cellular processes (e.g. tumor formation and angiogenesis, insulin resistance, adipogenesis and T-lymphocyte activation) and is deregulated in human diseases such as cancer and type 2 diabetes. These observations have attracted broad scientific and clinical interest in mTOR. This is highlighted by the growing use of mTOR inhibitors [rapamycin and its analogues (rapalogues)] in pathological settings, including the treatment of solid tumors, organ transplantation, coronary restenosis and rheumatoid arthritis. Here, we highlight and summarize the current understanding of how mTOR nucleates distinct multi-protein complexes, how intra- and extracellular signals are processed by the mTOR complexes, and how such signals affect cell metabolism, growth, proliferation and survival.

Sonic hedgehog is a protein that in humans is encoded by the SHH ("sonic hedgehog") gene.[5] Both the gene and the protein may also be found notated alternatively as "Shh". Sonic hedgehog is one of three proteins in the mammalian signaling pathway family called hedgehog, the others being desert hedgehog (DHH) and Indian hedgehog (IHH). SHH is the best studied ligand of the hedgehog signaling pathway. It plays a key role in regulating vertebrate organogenesis, such as in the growth of digits on limbs and organization of the brain. Sonic hedgehog is the best established example of a morphogen as defined by Lewis Wolpert's French flag model—a molecule that diffuses to form a concentration gradient and has different effects on the cells of the developing embryo depending on its concentration. SHH remains important in the adult. It controls cell division of adult stem cells and has been implicated in the development of some cancers.

Peroxisome proliferators include hypolipidemic drugs, herbicides, leukotriene antagonists, and plasticizers; this term arises because they induce an increase in the size and number of peroxisomes. Peroxisomes are subcellular organelles found in plants and animals that contain enzymes for respiration and for cholesterol and lipid metabolism. The action of peroxisome proliferators is thought to be mediated via specific receptors, called PPARs, which belong to the steroid hormone receptor superfamily. PPARs affect the expression of target genes involved in cell proliferation, cell differentiation and in immune and inflammation responses. Three closely related subtypes (alpha, beta/delta, and gamma) have been identified. This gene encodes the subtype PPAR-alpha, which is a nuclear transcription factor. Multiple alternatively spliced transcript variants have been described for this gene, although the full-length nature of only two has been determined.

Nerve growth factor (NGF) is a member of the neurotrophin family of secretary proteins that are involved in cell survival, growth and differentiation. It is important for the development and maintenance of both the sympathetic and sensory nervous systems. This pathway highlights how NGF binds to p75NTR or TrkA and activates the PI3K, Ras and PLC signaling pathways. NGF signals through at least two types of receptor; the low-affinity nerve growth factor receptor [LNGFR or p75 neurotrophin receptor (p75NTR)] and TrkA, a transmembrane tyrosine kinase. When NGF binds to TrkA, the receptor dimerizes and autophosphorylates its tyrosine kinase domain, which leads to the activation of PI3K, Ras, and PLC signaling pathways. Alternatively, p75NTR can form a heterodimer with TrkA which has higher affinity for NGF.

Epithelial to Mesenchymal Transition