signal transduction

• Transduction


  Cascades of molecular interactions relay signals from receptors to target molecules in cell
• Signal transduction


  • Usually involves multiple steps and multiple molecules
  • Multistep pathways can amplify a signal, a few molecules can produce a large cellular response
  • Multistep pathways provide more opportunities for coordination and regulation of responses
• Steps in signal transduction

  1. Addition or removal of phosphate groups

  2. Release of other small molecules
• Signal transduction pathway


  1. Binding of specific signalling molecules to a receptor in the plasma membrane triggers the first step

  2. Molecules which relay signal from receptor to response are mostly proteins

  3. Original signalling molecule isn't physically passed along signalling pathway, certain info is passed on

  4. At each step, signal is transduced to different form, usually changes shape in a protein
• Protein phosphorylation


  Protein kinases (enzymes) transfer phosphates from ATP to protein, normally causes protein activation
• Protein dephosphorylation


  Protein phosphatases remove phosphates from proteins, usually switches gene off
• Phosphorylation and dephosphorylation


  Acts as a molecular switch, turning activities on, off or up, down
• Phosphorylation cascade


  1. Active/inactive forms of proteins shown in different shapes

  2. Signal is transmitted by a cascade of protein phosphorylations each causing shape change in phosphorylated protein
• Second messengers


  Small, non-protein, water-soluble molecules or ions that easily spread throughout a cell by diffusion, participate in both pathways initiated by GPCR and RTK
• Cyclic AMP (cAMP)


  • One of the most widely used second messengers
  • Binding of epinephrine to the plasma membrane increases cAMP in cytosol
  • Adenylyl cyclase, an enzyme in the plasma membrane, converts ATP to cAMP in response to extracellular signal
  • cAMP can be broken down by phosphodiesterase to form AMP
• Cholera toxin


  • Activates G protein
  • Modified G protein is unable to hydrolyse GTP to GDP, is constantly switched on
  • Constant activation of adenylate cyclase and continuous production of cAMP
  • High cAMP levels activate the cystic fibrosis transmembrane conductance regulator (CFTR)
  • Causes dramatic efflux of Cl- ions and water from infected cells leading to watery diarrhoea
• Calcium ions (Ca2+)


  • More widely used than cAMP as a secondary messenger
  • Increased Ca2+ may cause many responses in animals: muscle cell contraction, exocytosis of molecules (secretion) and cell division
  • Normally much lower conc of Ca2+ in cell than outside
  • Usually higher conc of Ca2+ in ER than cytosol
  • Cytoplasmic calcium is actively pumped into ER and/or mitochondria to keep cytoplasmic conc of calcium ions low
• Inositol triphosphate (IP3)


  Pathway leading to release of calcium involves IP3 and diacylglycerol (DAG) as additional second messengers
• Calmodulin (CaM)


  • Very specific calcium modulated protein, contains 4 Ca2+ binding sites
  • Calcium binding ATPase (pumps Ca2+ out of cell) also activated by CaM, reduces cytoplasmic Ca2+ conc
• Signalling pathway leading to regulation of cellular activities

  1. Response may occur in cytoplasm or nucleus

  2. Many signalling pathways regulate synthesis of enzymes or other proteins, usually turning genes on or off in nucleus

  3. Final activated molecule in signalling pathway may function as a transcription factor
• Typical signalling pathway leading to regulation of gene expression in response to growth hormone

  1. Signalling molecule binds to receptor, leading to activation of phospholipase C

  2. Phospholipase C cleaves a plasma membrane phospholipid called PIP2 into DAG and IP3

  3. DAG functions as a second messenger

  4. IP3 diffuses through the cytosol and binds to IP3-gated calcium channel in ER membrane, causing it to open

  5. Calcium ions flow out of the ER down conc gradient, raising the Ca2+ level in the cytosol

  6. Calcium ions activate next protein in one or more signalling pathways
• Fine tuning of signalling pathway response

  • Amplify signal and response
  • Specificity of response
  • Overall efficiency of response, enhanced by scaffolding proteins
  • Termination of signal
• Scaffolding proteins


  Large relay proteins that other relay proteins are attached to, often increase efficiency of transduction by grouping together different proteins involved in same pathway