What is the biological role of signal transduction
- Cells receive signals from environment beyond plasma membrane
- Types of signals include antigens, hormones, neurotransmitters, light, touch, pheromones
- These signals cause changes in the cell’s composition and function
- Such as differentiation and antibody production, growth in size or strength, cell division (proliferation), migration
What are receptors
- A membrane-bound / soluble protein / complex
- Exerts a physiological effect after binding its natural ligand
- Receptors interact with signals and translate message to cell
What is protein kinase, phosphorylation and protein phosphatase
- PK: Enzymes that regulate biological activity of proteins by phosphorylation of AA with ATP as source of P, inducing conformational change from inactive to active form
- P: Addition of phosphate group to oneself
- PP: Enzyme that removes a phosphate group from the phosphorylated amino acid residue of its substrate protein
What are the 6 features of signal transducing systems
- Specificity
- Amplification
- Modularity
- Desensitisation / Adaptation
- Integration
- Localised response
What is specificity binding (1)
- Signal molecule fits binding site on its complementary receptors
- Other signals do not fit
What is amplification binding (2)
- Enzymes activate enzymes
- Number of affected molecules increases geometrically in enzyme cascade
- Epinephrine Cascade: Activation of GPCRs, adenyl cyclase and cAMP lead to drastic stimulation of glycogen degrading enzymes
What is modularity binding (3)
- Proteins with multivalent affinities form diverse signalling complexes from interchangeable parts
- Phosphorylation provides reversible points of interaction
- Example: Gated ion channels, NR, integrins
What is self-inactivation / desensitisation binding (4)
- Receptor activation triggers feedback that shuts off receptor or removes it from cell surface
- Enzyme linked membrane receptors (insulin)
What are typical ligands
- Small Ions: Ferric ion (bacterial ferric receptor)
- Organic Molecules: Adrenalin (epinephrine receptor)
- Polysaccharides: Heparin (fibroblast growth factor or ATIII)
- Peptides: Insulin (insulin receptor)
- Proteins: Vascular endothelial growth factor (VEGF receptor)
What are examples of 5 basic receptor types
- G protein coupled
- Enzyme linked
- Ligand-gated ion channels
- Nuclear receptors
- Integrins
What are G protein coupled receptors
- Indirectly activate enzymes that generate intracellular second messengers
- Activated G protein activates adenylyl cyclase and raises conc of secondary messenger cAMP
- cAMP stimulates cAMP dependent protein kinase to phosphorylate key target enzymes
- Examples: Epinephrine
What are enzyme linked receptors
- Extracellular ligand binding domain and intracellular catalytic domain
- Example: Tyrosine kinase activity, insulin receptor, epidermal growth factor receptor
What are ligand gated ion channel receptors
- Channels of plasma membrane that open and close in response to binding / membrane potential
- Simplest signal transducers
- Regulate transport of ions
- Nerve Signalling: Open Ca channels, Ca causes release of acetylcholine, opens ligand channels on receiving cells
What are nuclear receptors
- Bind specific ligands and alter rate at which genes are transcribed / translated
- Diffuses across membrane, hormone binds receptor in nucleus
- HR complexes attract other activators / repressors
- Example: Thyroid, vit D, steroid, nitric oxide
What is integration binding (5)
- System receives multiple signals and produces a unified response
- Regulatory outcome results from integrated input from both receptors
- Different signalling pathways converse
What is localised response binding (6)
- When enzyme that destroys intracellular message is clustered with message producer
- Message is degraded before it can diffuse to distant points
- Response is local and brief
Describe the importance of cAMP and cGMP as secondary messengers
cAMP
- Secondary messenger, allosterically activates a variety of enzymes including
- cAMP-dependent protein kinase (PKA) is phosphorylated / activated
- Causes cellular response and release of enzymes / hormones to initial stimulus
cGMP
- Alternative secondary messenger
- Regulates glycogenolysis / apoptosis / vasodilation
What are integrin receptors
- Mediate cell adhesion, extracellular domain interacts with Arg-Gly-Asp containing ECM proteins (collagen, fibrinogen, fibronectin, and others)
- This triggers cytoskeleton rearrangement and gene expression
