Signal Transduction Pathways (College Board AP Biology)

• Signal transduction is the series of steps that govern the appropriate response by the cell
• These are triggered by the binding of the ligand to its specific receptor

Transmembrane Receptor Proteins

• Receptors that are located in the cell membrane have an external binding site and an internal region which extends into the cytoplasm
  • These are transmembrane proteins as they extend right across the width of the membrane
• Transmembrane receptors are characterized by:
  • Hydrophilic amino acid regions at either end of the protein that are contact with the aqueous solution inside and outside the cell
  • A hydrophobic amino acid region within the membrane that is in contact with the hydrophobic tails of the phospholipids inside the cell membrane
• Some ligands bind to these receptors instead of entering the cell cytoplasm

Transmembrane Receptor Diagram

The cell surface membrane has many different components, including transmembrane proteins, e.g. glycoproteins, that function as receptors

Intracellular receptors

• Nonpolar, hydrophobic ligands, eg. steroid hormones, can diffuse through the phospholipid bilayer
• These ligands bind to receptors in the cytoplasm or on the DNA in the nucleus of the cell
  • Steroid hormones such as estradiol will bind to the receptor molecule and activate it so that protein synthesis is initiated

Intracellular Receptor Diagram

Estradiol is a steroid hormone that diffuses across the cell membrane and binds to an intracellular receptor in the cytoplasm of target cells

• When a ligand binds to either the transmembrane receptor or the intracellular receptor, a cascade of events follows which leads to a resulting change in cell activity
• The sequence of events is called the signal transduction pathway
  • Different ligands and different receptors trigger different signal transduction pathways
• All signal transduction pathways follow the same basic process
  • Binding with the receptor
    • For a transmembrane receptor:
      • A ligand binds to the extracellular region of the transmembrane receptor protein, causing a change in shape of the internal region of the protein
    • For an intracellular receptor:
      • A ligand binds to an intracellular receptor, forming a ligand-receptor complex
  • Signal transduction through a multistep pathway of events
    • For a transmembrane receptor:
      • Transmembrane proteins initiate a signal transduction pathway which involves phosphorylation events and a second messenger
      • Cyclic AMP (cAMP) is an example of a second messenger
    • For an intracellular receptor:
      • Intracellular ligand-receptor complexes are activated to follow a signal transduction pathway
  • Cellular responses which may include:
    • Regulation of gene expression through control of transcription or translation
    • Change in metabolic activity
    • Regulation of enzyme activity
    • Cell death
    • Rearrangement of the cytoplasm of the cell
    • Regulation of proteins, eg. channels in the plasma membrane

Signal Transduction Diagram

Ligands can bind to transmembrane receptors, resulting in signal transduction and a cellular response

The Second Messenger Model

• Epinephrine binds to specific receptors on the membrane of liver cells
• This causes the enzyme adenylyl cyclase to change shape and become activated
• Active adenylyl cyclase catalyzes the conversion of ATP to the second messenger, cyclic AMP (cAMP)
• cAMP binds to protein kinase A enzymes, activating them
• Active protein kinase A enzymes activate phosphorylase kinase enzymes by adding phosphate groups to them
• Active phosphorylase kinase enzymes activate glycogen phosphorylase enzymes
• Active glycogen phosphorylase enzymes catalyze the breakdown of glycogen to glucose
  
  • This process is known as glycogenolysis
• The enzyme cascade described above results in the release of glucose by, eg. cells in the liver, to increase blood glucose concentration

Role of Second Messenger Cyclic AMP 

Cyclic AMP acts as a second messenger in the action of the hormone epinephrine