Signaling ligand

Once released from the cell of origin, the signal ligand must travel to its site of action. For the classical endocrine hormones this means via the bloodstream. Given that blood plasma is approximately 94% water, the physical nature of the hormone is important. Peptides are hydrophilic and so circulate unbound to any other molecule whereas... 

Binding of extracellular messengers to the receptor opens an ion channel, which, in this case, is a part of the receptor. The receptor and the ion chaimel form one structural unit (see 16.4.3, Acetylcholine receptor). This permits very fast translation of the signal ligand binding" into the signal ion passage". 

Opens or closes in response to concentration of signal ligand (S) or membrane potential. 

Ligand-dq aidait transcriptional activation flinction core (AF2) Nuclear localization signal Ligand-indq aidait transcriptional activation fimction (AFI) Silencing fLinction... 

Apart from the classical, well-known hormones listed in Fig. 4.1, other compounds are also used as signaling ligands for the activation of certain nuclear receptors. These ligands may be synthesized intracellularly as normal metabolites such as fatty acids and bile acids and they may be derived from foreign lipophilic substances like drugs. 

Ephrins are cell-surface signaling ligands whose receptors (Ephs) are receptor tyrosine kinases. 

NMR-based screening methods can be classified into two groups according to the source of the observed signals, ligand-detected NMR and protein-detected NMR. 

Question What kinds of extracellular molecules act as signaling ligands for receptors ... 

A wide range of extracellular molecules can act in this way. They include metal ions, low molecular weight compormds (e.g., amino acids and metabolites derived from them), peptides, and proteins. In particular physiological contexts, the signaling ligands for specific receptors are variously referred to as hormones,... 

It is common for the substrates of protein kinases to include other protein kinases. This provides a mechanism for amplifying the initial signal of binding of a signaling ligand to its receptor, known as a protein kinase cascade. A protein kinase cascade occurs when activation of one protein kinase leads to phosphorylation (and consequent activation) of a second kinase, followed by phosphorylation and activation of a third kinase, etc. 

Although G protein-coupled receptors have a common molecular architecture (Sec. 6.3), they respond to a diverse range of signaling ligands, including proteins, small peptides, and derivatives of amino acids and fatty acids. 

Heterotrimeric G proteins are composed of a, P, and y polypeptide chains. Usually, the a and y chains are anchored to the inner leaflet of the plasma membrane by Upid anchors that consist of a fatty acid that is linked to a cysteine side chain by a thioester bond. As shown schematically in Fig. 6-13, the binding of a signaling ligand leads to exchange of a molecule of GDP for a molecule of GTP, bound to the Ga subunit. Concurrently, the Ga subunit dissociates from the GpGy subunit. This allows both the Ga and the GPGy subunits to interact with other signaling molecules. 

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