Last updated: April 27, 2022
Summary
In signal transduction, extracellular signals are converted into intracellular signals: A signaling molecule (ligand) reaches its target cell and binds to a specific receptor. This activates a signaling cascade involving intracellular enzymes and molecules (second messengers), which again leads to a specific reaction. Via signal amplification, the number of signaling molecules is increased at every step of the signal cascade.
Terminology
Overview
Receptors
Ligands of the intracellular receptors (Progesterone, Estrogen, Testosterone, vitamin D, Cortisol, Aldosterone, Thyroid hormones): PET Da CAT
G protein-coupled receptors
G protein-coupled receptors (GPCRs) are the largest family of membrane receptors. The action of GPCRs depends on three elements: the receptor, the G protein, and the effector molecule.
Gs proteins activate adenylyl cyclase, whereas Gi proteins inhibit adenylyl cyclase.
Receptor tyrosine kinases (RTKs)
Receptor tyrosine kinases are transmembrane receptors that are generally activated by ligand-induced dimerization and autophosphorylation of cytoplasmic tyrosine residues, which triggers activation of downstream signaling cascades.
Ligands of the tyrosine kinase receptors (TYRosine kinase, INSULin, GROWth factors): “I'm TYRed of your INSULts, GROW up!”
Non-receptor tyrosine kinases
Ligands of the non-receptor tyrosine kinase (Prolactin, Interleukins/IFN, Growth hormone, G-CSF, Erythropoietin, Thrombopoietin): PIGGLET
Receptor serine/threonine kinases
Since most ligands of ligand-gated ion channels are neurotransmitters, only a short overview is provided here.
Second messengers
Second messengers are small molecules that mediate the intracellular response to an extracellular stimulus.
Synthesis
Effects
cAMP activates ; protein kinase A (PKA).
Degradation
cAMP is degraded by phosphodiesterase to adenosine monophosphate (AMP).
Examples of ligand hormones
Soluble guanylate cyclase is activated by nitric oxide.
The second messengers cAMP and cGMP are degraded and inactivated to AMP and GMP by various phosphodiesterases (PDE). A decrease in cAMP or cGMP causes contractions in smooth muscles. PDE inhibitors are used in the treatment of pulmonary hypertension (PDE-4 inhibitor roflumilast) and erectile dysfunction (PDE-5 inhibitor sildenafil).
Ligands of the guanylate cyclase (GMP, BNP, EDRF, ANP): GruMPy BEA
Nitric oxide (NO) has a half-life of only a few seconds. It is not stored by the body but is synthesized as a result of activation. Nitrate drugs stimulate the formation and release of NO. Relaxation of smooth muscle cells in vessel walls leads to the dilation of coronary arteries, pulmonary arteries, and peripheral veins. Peripheral vasodilation leads to a decrease in cardiac preload.
Gq proteins activate phospholipase C, which cleaves the second messengers IP3 and DAG from PIP2. These, in turn, activate PKC.
Ligands of the phosphoinositol signaling pathway (TRH, Vasopressin, Angiotensin, GnRH, Oxytocin, Gastrin, Histamine): TRy VAn GOGH
Ca2+ mediates the effect of other second messengers such as IP3 and DAG via PKC activation. It also functions as a second messenger by acting directly, i.e., without activating another signaling molecule.