The ability of cells to perceive and correctly adapt to their microenvironment is critical for maintaining normal homeostasis and development as well as for appropriate response to external stimuli. Receptors on the cell surface bind extracellular signaling molecules and transfer that signal to the interior of the cell, setting in motion a cascade of enzymatic reactions and secondary messenger molecules, ultimately altering cell function in response to the extracellular message.
For example, G protein-coupled receptors (GPCRs), large family of membrane receptors that are found on the surface of a cell, individually bind to and become activated by a specific ligand which can range in size from small neurotransmitters or lipids to large protein hormones. When a specific GPCR is activated a conformation change is induced in the receptor protein which carries through to the portion of the protein on the intracellular side of the membrane, ultimately causing the release of the Gs alpha subunit into the cytoplasm where it activates adenylate cyclase and catalyzes the conversion of ATP to cyclic AMP (cAMP). cAMP is a secondary messenger molecule that can lead to the activation of a variety of enzymes, proteins, and ion channels. One of the most prominent enzymes activated by cAMP is PKA. Once activated PKA in turn can phosphorylate a large number of enzymes and transcription factors propagating a vast array of downstream effects. The specificity of the signal pathway activated by an individual GPCR can be refined by the formation of multiprotein complexes involving the receptor, adenylate cyclase and specific effector proteins, allowing the signal to be directed along a particular pathway so the cell responds in a defined way.
Signal transduction pathways are complex and involve many individual components, each providing the opportunity for feedback, signal amplification, regulation, and cross talk interactions where multiple pathways intersect. This complexity, where biology meets chemistry, allows organisms to respond quickly on the cellular level to all sorts of environmental and chemical inputs, forming the basis of all life.
Arbor Assays provides convenient, highly sensitive assay kits to directly quantitate a variety of intracellular second messenger molecules including cAMP (EIA, CLIA), cGMP (EIA, CLIA), Nitric Oxide and PGE2 as well as a kit to measure the activity of the important signal cascade enzyme PKA. Understanding how extracellular factors such as disease states, stress, environment and even aging affect cells on the chemical level can provide insight into potential treatments and provide a way to measure their effects.