Signal transduction

Last updated: April 27, 2022

Summarytoggle arrow icon

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.

Terminologytoggle arrow icon

Overviewtoggle arrow icon

Receptorstoggle arrow icon


Intracellular receptors

Ligands of the intracellular receptors (Progesterone, Estrogen, Testosterone, vitamin D, Cortisol, Aldosterone, Thyroid hormones): PET Da CAT

Cell surface receptors

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.

Overview of main effects
Receptor types and their connected G proteins
Gq proteins Gs proteins Gi proteins Main effects
Sympathetic α
  • α1
  • N/A
  • α2

Sympathetic β

  • N/A
  • β1
  • β2
  • β3
  • N/A

Parasympathetic muscarinic

  • N/A
  • M2


  • H1
  • H2
  • N/A


  • D1
  • D2


  • V1
  • V2
  • N/A
  • V1: increases tone of vascular smooth muscle
  • V2
    • Increases:
      • Upregulation of aquaporin-2 in renal collecting tubules
      • Water permeability and reabsorption
      • Release of vWF

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.

  • Examples of ligands: insulin, growth factors (e.g., EGF, IGF, FGF, TGF)
  • Receptor structure:
    1. Extracellular domain
    2. Single transmembrane domain
    3. Intracellular domain with tyrosine kinase activity
  • Activation principle
    1. Ligand binding to the extracellular domain results in receptor dimerization.
    2. The two adjacent tyrosine kinase domains phosphorylate one another to tyrosine residues (autophosphorylation).
    3. Increased kinase activity through autophosphorylation
    4. A number of different signal transduction molecules with SH2 domains bind to the phosphorylated tyrosine residues and are activated → activation of various effectors of different signaling pathways
  • Examples of effectors

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

Ligand-gated ion channels

Since most ligands of ligand-gated ion channels are neurotransmitters, only a short overview is provided here.

Second messengerstoggle arrow icon

Second messengers are small molecules that mediate the intracellular response to an extracellular stimulus.

cAMP (cyclic adenosine monophosphate) and protein kinase A



cAMP activates ; protein kinase A (PKA).


cAMP is degraded by phosphodiesterase to adenosine monophosphate (AMP).

Examples of ligand hormones

cGMP (cyclic guanosine monophosphate)

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

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.

IP3 and DAG

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+ as a second messenger

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.

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 Evidence-based content, created and peer-reviewed by physicians. Read the disclaimer