Signal transduction (including basic principles, receptors and channels, second messengers, signal transduction pathways)
signal transduction, hormones, receptors

Signals

  • Endocrine: long distance, hormones secreted into blood. Eg. The endocrine hormones.
  • Paracrine: local mediators, hormones released into extracellular fluid. Eg. Growth factors, histamine, NO
  • Neuronal: travels through axons, then neurotransmitters across synapse.
  • Contact-dependent: cells influencing their neighbors by contact. Eg. Delta-Notch: developing neurons (Delta signal) inhibiting neighboring epithelial cells (Notch receptor) from developing into neurons.

Receptors and their signal transduction pathways

  • Intracellular: for signal molecules that can cross the plasma membrane. Eg. Steroids, NO.
  • Ion channel linked: binding of receptor to ion channel causes it to open or close. Eg. Neural transmitters.
  • G protein linked: activates G protein (GDP → GTP), which then activate enzymes (Adenylyl cyclase, phospholipase C) that generate secondary messengers (cAMP, IP3, DAG), or the G protein can simply open/close ion channels.
    • Adenylyl cyclase → cAMP → cAMP-dependent protein kinase (PKA). Eg. Adrenaline.
    • Phospholipase C →
      • IP3 → Ca2+ → calmodulin → CaM kinase
      • DAG → protein kinase C (PKC). The C stands for Calcium, because it needs it to be active.
      • Eg. Thrombin.
  • Enzyme linked: instead of linking to G protein, it links to an enzyme (Receptor tyrosine kinase, cytokine receptor, receptor ser/thr kinase).
    • Receptor tyrosine kinase →
      • Adaptor protein → ras activating protein → ras → MAP kinase cascade. Eg. Mitogens.
      • Adaptor protein → PI 3-kinase → protein kinase B (PKB). Eg. Insulin stimulation of glycogen synthesis.
    • Cytokine receptor → JAK (Janus kinase) → STAT (signal transducers and activators of transcription). Eg. Interferons.
    • Receptor serine/threonine kinase → SMAD (cytoplasmic gene regulatory proteins named after nematode Sma and fly Mad). Eg. TGF-β

Second messengers

  • First messenger = the original signal molecule. Eg. Hormone.
  • Second messenger = intracellular signal molecule. Eg. cAMP, IP3, DAG.
  • Original signal gets transduced (signal transduction) into secondary messenger.
  • Second messengers diffuse throughout the cell, affect their targets, then get degraded.