9.2 Propagation of the Signal

Cells communicate through intricate signal transduction pathways. These pathways begin when signaling molecules bind to receptors, triggering cascades of biochemical reactions. The process involves phosphorylation, second messengers, and complex regulatory mechanisms.

Signal transduction allows cells to respond to their environment and coordinate with other cells. It's crucial for processes like growth, development, and homeostasis. Understanding these pathways helps explain how cells function and how diseases can arise from signaling errors.

Signal Transduction

Ligand binding and signal transduction

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• Signaling molecules (hormones, growth factors, neurotransmitters) bind to specific receptors on the cell surface or within the cell
• ###receptor-ligand_binding_0### induces a conformational change in the receptor protein
  • Conformational change may involve receptor dimerization or oligomerization
  • Binding sites for intracellular signaling molecules may be exposed or created
• Activated receptors initiate signal transduction cascades within the cell
  • Biochemical reactions amplify the signal and relay it to specific cellular targets (enzymes, transcription factors, ion channels)
• Specific signal transduction pathway activated depends on the receptor and ligand type
  • G protein-coupled receptor (GPCR) pathways
  • Receptor tyrosine kinase (RTK) pathways
  • Ion channel-linked receptor pathways

Phosphorylation in signaling pathways

• Addition of a phosphate group (PO4) to a molecule, usually a protein, catalyzed by protein kinases
  • Kinases transfer phosphate from ATP to specific amino acid residues (serine, threonine, tyrosine) on target proteins
• Phosphorylation alters conformation, activity, and function of target proteins
  • Activates or inactivates enzymes
  • Modulates protein-protein interactions
  • Changes protein localization within the cell
• Phosphorylation is reversible; phosphate groups removed by phosphatases
  • Balance between kinase and phosphatase activity allows precise regulation of signaling
• Phosphorylation cascades amplify and propagate signals within the cell
  • One activated kinase phosphorylates and activates multiple downstream kinases or effector proteins
  • Small initial signal triggers a large cellular response (signal amplification)
• Phosphorylation enables crosstalk and integration of different signaling pathways
  • Proteins phosphorylated by multiple kinases allow fine-tuning of cellular responses based on integration of various signals

Second messengers for signal amplification

• Small, diffusible molecules that relay signals from receptors to intracellular targets
  • Cyclic AMP (cAMP)
  • Calcium ions (Ca2+)
  • Inositol trisphosphate (IP3)
• Generated or released in response to receptor activation
  • GPCRs activation leads to cAMP production by adenylyl cyclase or Ca2+ release from endoplasmic reticulum
• Amplify signals by activating multiple effector proteins
  • cAMP activates protein kinase A (PKA), which phosphorylates numerous downstream targets
  • Ca2+ binds to and activates proteins like calmodulin, regulating many cellular processes
• Diffuse throughout the cell, allowing signal propagation to different cellular compartments
  • Activation of targets far from initial site of receptor activation
• Different second messengers activate distinct signaling pathways, diversifying cellular responses
  • cAMP and Ca2+ activate different kinases and transcription factors, leading to distinct changes in gene expression and cellular behavior
• Combination of different second messengers and their spatiotemporal dynamics allows complex and specific cellular responses to extracellular signals
  • Interplay between second messengers (cAMP and Ca2+ levels) fine-tunes cellular responses based on integration of multiple signals

Signal Regulation and Integration

• Feedback regulation mechanisms control the intensity and duration of signaling
  • Negative feedback loops can attenuate or terminate signals
  • Positive feedback loops can enhance and prolong signaling responses
• Signal termination is crucial for maintaining cellular homeostasis and preventing overstimulation
  • Involves processes such as receptor internalization, degradation of signaling molecules, and activation of inhibitory proteins
• Signal integration allows cells to process and respond to multiple inputs simultaneously
  • Occurs at various levels of signaling pathways, from receptors to downstream effectors
• Scaffold proteins play a role in organizing signaling components
  • Facilitate the assembly of multi-protein signaling complexes
  • Enhance the efficiency and specificity of signal transduction
• Signal specificity is achieved through various mechanisms
  • Unique combinations of receptors and signaling molecules
  • Spatial and temporal regulation of signaling components
  • Cell type-specific expression of signaling proteins