After reception of a signal molecule, transduction involves a pathway of reactions, with each molecule in the pathway causing a change in the next molecule, eventually activating a response. Overview:

• reception
  
  
  In reception, a signal molecule binds to a receptor protein, causing it to change shape.

  
  

• intracellular receptors
  
• membrane receptors:+ G-protein-linked receptors+ receptor tyrosine kinases
• ion channel receptors

  Review:
  
  

  Steroid hormones such as testosterone are made from the lipid cholesterol.

  The hydrophobic steroids can cross the lipid bilayer of the plasma membrane to bind intracellular receptors.

  In this case the response is to stimulate DNA in the nucleus to produce proteins.

  
  
  
  G-protein-linked receptors.
  • The G-protein is inactive when it is attached to a GDP (guanosine diphosphate) molecule.
  • A signal molecule binds to the receptor, which changes shape and binds to the inactive G-protein. A GTP molecule displaces the GDP, and activates the G-protein.
  • The activated G-protein binds to another enzyme and activates it to initiate a cellular response.
  • The G-protein hydrolyzes the GTP and returns to an inactive state.
  
  
  
  • Receptor tyrosine kinases contain multiple tyrosines and are inactive in the monomer state.
  • Binding of signal molecules, such as insulin, causes 2 monomers to form a dimer.
  • ATP donates a phosphate to each of the tyrosines.
  • Relay proteins bind to the phosphorylated tyrosines, and trigger different cellular responses.
  
  
  
  Ion channel receptors respond to ligands such as neurotransmitters to open sodium gates and relay nerve impulses.
  • The gate is closed.
  • A ligand binds to the receptor and the gate opens, Na^+ ions flow through the channel.
  • The ligand dissociates from the cell, closing the gate.

    Note the difference with facilitated diffusion.

   
   
   
   
• transduction
  
  
  In transduction, signals are relayed from receptors to target molecules, as in a cascade. Some transduction pathways involve small molecules called second messengers.

  
  

• cyclic AMP (cAMP)
  
• calcium

  Review:
  
  

  Phosphorylation cascade.

  A series of molecules in a signal pathway are phosphorylated and activated in turn.

  The phosphates are donated from ATP, catalyzed by enzymes called kinases.

  Each phosphorylation acts as a switch, turning on a response.

  
  
  
  Cyclic AMP (cAMP) is made from ATP by adenylyl cyclase, an enzyme embedded in the plasma membrane.

  Many G-proteins trigger the formation of cAMP, which then acts as a second messenger.

  
  
  
  A first messenger (e.g., epinephrine) phosphorylates and activates a G-protein.

  This in turn activates adenylyl cyclase to convert ATP to cAMP.

  cAMP acts as a second messenger by activating other proteins in a phosphorylation cascade to yield a response.

  
  
  
  Calcium as second messenger.

  Protein pumps maintain a Ca^2+ gradient across the plasma membrane and the membranes of the ER and mitochondrion.

  An increase in Ca^2+ concentration in the cytosol often acts as a second message in processes such as muscle contraction and cell division.

  Muscle contraction:

   
   
   
   
• response

Review:

Signal amplification.

Epinephrine acts through a G-protein-linked receptor to activate a succession of relay molecules, including the second messenger cAMP.

This amplifies the signal: one receptor protein can activate about 100 molecules of G protein.

Each enzyme in the cascade can act on many molecules of the next molecule, resulting in a 100 million -fold amplification in the response.

Review:

Nuclear response.

A growth factor triggers a phosphorylation cascade.

The last kinase in the cascade enters the nucleus and activates a transcription factor.

This in turn stimulates a gene to synthesize an mRNA molecule, which then directs the synthesis of a protein in the cytoplasm.