20 Cell Signalling

• Cell Signalling


  • Cell signalling involves three main stages: ligand-receptor interaction (also known as reception), signal transduction, and cellular response
  • Cell signalling can trigger diverse cellular responses depending on the type of signal molecule, signal transduction pathway, and cell
  • Cells employ feedback mechanisms to regulate signalling processes, with negative feedback helping to maintain homeostasis
• Cell signalling is the fundamental process by which specific information is transferred from the cell surface to the cytosol and ultimately to the nucleus, leading to changes in gene expression
• Ligand (signal molecule) binds to a specific ligand-binding site of a protein receptor to form a ligand-receptor complex
• Types of Receptors

  • G-protein coupled Receptor
  • Receptor Tyrosine Kinase (RTK)
  • Ion Channel Receptor (not in syllabus)
• Ligand-binding site is structurally complementary to the ligand
• Receptor – protein that binds and transduces the message of the signal molecule into a cellular response
• Overview of the Stages of Cell Signalling

  1. Stage 1: Reception

  2. Stage 2: Signal Transduction

  3. Stage 3: Cellular Response
• Types of Cell Communication

  • Direct communication which involves physical contact between interacting cells
  • Indirect communication which involves extracellular chemical messengers or signal molecules that bind to receptors
• Signal transduction – a series of steps by which signals are conveyed into the target cell where they are transformed into a cellular response
• Regulation of Blood Glucose Concentration & Specific Examples of Receptors

  1. Glucagon and G-protein signalling

  2. Insulin and Receptor Tyrosine Kinase (RTK) signalling
• Ligand – a signal molecule that binds specifically to another molecule, usually a receptor. Known as extracellular chemicals/first messengers
• Ligand


  Signalling molecule (e.g. hormones, growth factors) that binds to a specific ligand-binding site of a protein receptor
• Ligand-receptor interaction

  Ligand binds to a specific ligand-binding site of a protein receptor to form a ligand-receptor complex
• Ligand-receptor interaction


  Specific due to ligand being complementary in shape and charge to the extracellular ligand-binding site of the receptor, initiating a cellular response in that specific target cell
• Binding of ligand to protein receptor

  Causes a conformational change in the protein receptor which initiates signal transduction
• Signal transduction

  Signal is converted to a form that can bring about a specific cellular response. Can occur in a single step or in a series of multiple steps in a signal transduction pathway
• Ligand-binding site


  Structurally complementary to the ligand
• Signal transduction pathway

  Mediated by intracellular signalling proteins such as kinases (that carry out phosphorylation), or small molecules and ions such as cAMP (secondary messengers)
• Protein phosphorylation and dephosphorylation are types of post-translational modifications that help regulate protein function
• Phosphorylation cascade


  Sequence of events where one enzyme phosphorylates another, causing a chain reaction leading to the phosphorylation of thousands of proteins
• Function of a signal transduction pathway

  • To change the behaviour of a cell
• Signal amplification produces a large number of an intracellular mediator from a relatively small number of extracellular signals
• Many relay molecules in signal-transduction pathways are protein kinases
• Signal-transduction pathways may involve a phosphorylation cascade where protein kinases successively add a phosphate group to activate the next protein in line
• A small number of extracellular signal molecules can activate a large amount of intracellular molecules and produce a large cellular response in a signal transduction pathway
• Most proteins are activated by phosphorylation and deactivated by dephosphorylation
• Types of receptors

  • Cell surface receptors
  • Intracellular receptors
• Protein phosphorylation

  Addition of phosphate groups to proteins, a major mechanism of signal transduction
• Signal transduction pathway

  1. Starts after reception

  2. Involves multiple steps

  3. Involves phosphorylation cascade

  4. Involves signal amplification
• Protein dephosphorylation

  Removal of phosphate groups from proteins, a way of deactivating proteins
• Protein kinases add phosphate groups from ATP to proteins during phosphorylation, while protein phosphatases remove phosphate groups from proteins by hydrolysis during dephosphorylation
• Protein phosphatases turn off the signal-transduction pathway in the absence of the extracellular signal, shutting down the signalling pathway and cellular response
• Signal molecule binding to receptor protein

  Causes a conformational change that allows the receptor protein to function as a transcription factor
• Signal transduction

  Series of changes in cellular proteins that converts an extracellular chemical signal to a specific intracellular response
• Reception in signal transduction pathway

  Signal molecule binds to the extracellular ligand-binding site of receptor protein, causing a conformational change in the intracellular domain of receptor protein, activating it to interact with other cellular molecules
• Activation of adenylyl cyclase by active G protein and activation of protein kinase A by cyclic AMP do not result in signal amplification
• Signal amplification


  At each step, one molecule acts on many other molecules, producing a large amount of the final product
• Signal transduction can proceed even with very little amount of signal molecules/receptors at the start
• Same cells

  Can have the same response to different signals
• Different cell types


  Can have different responses to the same signal