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Cyclic GMP: Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed)

Intracellular Signaling Cascades

JoVE 10721

Intracellular signaling cascades amplify a signal originating extracellularly and directs it to its intended intracellular target resulting in transcription, translation, protein modifications, enzyme activation, cellular metabolism, mitosis, and/or apoptosis.

The most basic of signaling cascades involves the activation of second messengers and the release of kinases. Kinases activate or deactivate proteins and enzymes by adding a phosphate group to them. Phosphatases remove phosphate groups resulting in the deactivation or reactivation of proteins. The cyclic AMP (cAMP) pathway is named for its second messenger, cAMP. This pathway is most often initiated when a ligand binds to a G-coupled protein receptor. The G-protein decouples from the receptor and triggers adenylate cyclase to synthesize cAMP from ATP. For each ligand-receptor interaction, multiple cAMP molecules are generated—amplifying the signal. cAMP activates protein kinase A (PKA). PKA is a tetramer molecule with two regulatory subunits and two active subunits. When four cAMP molecules interact with a PKA molecule, it releases the two active subunits. These PKA subunits phosphorylate target proteins and enzymes. In the case of gene expression, PKA activates CREB, a transcription factor in the nucleus. The steps that precede the intracellular signaling cascade that is the lig

 Core: Cell Signaling

Paracrine Signaling

JoVE 10716

Paracrine signaling allows cells to communicate with their immediate neighbors via secretion of signaling molecules. The signal only triggers a response in nearby target cells as the signal molecules degrade quickly or are inactivated by nearby cells if not taken up. Prominent examples of paracrine signaling include nitric oxide signaling in blood vessels, synaptic signaling of neurons, the blood clotting system, tissue repair/wound healing, and local allergic skin reactions. One of the essential paracrine signaling molecules is the gas nitric oxide (NO). Nitric oxide is produced by a family of enzymes known as nitric oxide synthases. Blood vessels contain several layers of cells. The innermost layer of cells is the endothelium. Endothelial cells have nitric oxide synthase, which produces nitric oxide that diffuses in all directions. The nitric oxide that reaches the blood does not contribute to signaling but immediately reacts with biochemicals, such as hemoglobin. Nitric oxide molecules that diffuse in the opposite direction, towards the next layer of the blood vessel, participate in some important signaling. The layer just exterior to the endothelium is made up of smooth muscle cells. The function of smooth muscle cells is to contract. When these cells contract, they clamp down on the blood vessel, narrowing its diameter and consequently rais

 Core: Cell Signaling

Coronary Progenitor Cells and Soluble Biomarkers in Cardiovascular Prognosis After Coronary Angioplasty

1Experimental Metabolism and Clinical Research Laboratory & Regenerative Medicine and Tissue Engineering Laboratory, 2Hemodynamics Unit, Cardiology Department, Centro Médico Nacional "20 de Noviembre" ISSSTE, 3Laboratorio de Biología del Desarrollo y Teratogénesis Experimental, Hospital Infantil de México Federico Gómez

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JoVE 60504

 JoVE In-Press
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