Overview

Cells communicate by a variety of chemical signals

• Example 1 : Hormones, such as insulin. Produced in one tissue, travel through bloodstream, interact with certain cells to change cell activity.
  
• Example 2 : Neurotransmitters, such as dopamine. Released by one nerve cell (neuron), travels very short distance to adjacent neuron, stimulates nerve cell activity.
  

The three stages of cell signaling are reception, transduction, and response

• View diagram showing overview of cell signaling ( protected)
• Explore types of cell responses that can be triggered by signal transduction: examples include conversion of glycogen to glucose, rearrangement of the cytoskeleton, or turning on a gene. (Campbell website activity)

Case Study: G-protein Linked Receptors

• Signaling pathways can be of several different types, including:
  
  • G-protein linked receptors
  • Tyrosine-kinase receptors
  • Ion-channel receptors
• Examine G-protein-linked receptors as a case study (see text fig. 11.6)
• View diagram of a G-protein receptor system ( protected)
• Three components: all allosteric proteins that can change shape in response to signal:
  
  1. Receptor protein
     • spans plasma membrane.
     • Has receptor site on outside, binding site for G-protein on inside.
     • Examine the variety of signal receptors (Campbell website activity)
  2. G-protein
     • Loosely attached to inner membrane.
     • Acts like on-off switch.
     • Inactive form when bound to GDP.
     • Active form when bound to GTP.
     • G-protein soon breaks GTP down to GDP, so "on" state switches back to "off".
  3. Target
     • usually a membrane-bound enzyme.
     • Enzyme is inactive until activated by active G-protein.
• View animation showing steps in G-protein linked signaling.
• Examples of signaling pathways that use G-proteins:
  
  • Many hormone receptors
  • Many neurotransmitters
  • Vison and smell in humans
• Other applications:
  • Many bacterial infections (botulism, cholera, etc.) produce toxins that interfere with G-proteins, leading to disease symptoms
    
  • As many as 60% of all medicines sold today act by influencing G-protein pathways

Some Features of Signal-Transduction Pathways

1. Second Messengers

• Not all signaling molecules are proteins. Some are small molecules.
  
• Example: cyclic AMP . View structure of c-AMP. ( protected)
• cAMP is produced from ATP by enzyme adenyl cyclase (often activated by G-protein).
• When adenyl cyclase activity inside cell rises, usually activates a protein kinase, which in turn phosphorylates other kinases.
  
• Cyclic AMP acts like an intracellular hormone, stimulating variety of effects that differs from tissue to tissue.
• Ca⁺⁺ ions also act as a second messenger.
• Explore second messengers (Campbell website activity)

2. Protein phosphorylation

• Many enzymes can exist in inactive ("off") and active ("on") states.
  
• Typical activation mechanism is to add a phosphate group from ATP (or GTP etc.)
• Activation requires another enzyme, called a protein kinase.
• Cells have many different protein kinases, each specific for a certain enzyme.
• Explore protein kinases (Campbell website activity)
• Kinases are often linked in several steps: Kinase 1 activates kinase 2, kinase 2 activates kinase 3, etc. to final target.
• View activation cascade ( protected) text Fig. 11.10

3. Amplification

• Why do cells use multi-step pathways? One major reason = amplification.
  
• Each activated component can turn "on" many different target molecules.
• The more steps involved, the bigger the final number of activated products = activation cascade.
• View diagram showing how numbers grow ( protected) text Fig. 11.15