Signal Transduction

Two immediate receptor responses upon ligand binding
• Conformational change of the individual receptor protein.
• Clustering/oligomerization of multiple ligand-bound receptors.
Either mechanism initiates a pre-programmed intracellular signaling cascade.
Conceptual significance: these are the universal "ON" switches that translate an extracellular cue into intracellular biochemistry.

Cells are simultaneously exposed to many extracellular cues (hormones, growth factors, neurotransmitters, etc.).
Therefore, multiple signaling pathways can be active at the same time within a single cell.
Cells must integrate all active pathways to generate a coordinated response that matches the overall environmental context.
• Integration can be additive, synergistic, or antagonistic.
• Crosstalk mechanisms (shared second messengers, kinase cascades, scaffold proteins) underlie this integration.

Signal transduction pathways typically generate amplification—a small extracellular event drives a large intracellular outcome.
Example:
• Epinephrine: 1 epinephrine molecule binding 1 receptor → hundreds of millions (≈10^8) of glucose molecules released from glycogen.
Practical implication: high sensitivity; cells respond to very low ligand concentrations.

Ligand-gated ion channels (previous lecture; chiefly neurotransmitter receptors).
• Fast, millisecond responses.
Plasma-membrane receptors (focus of upcoming sections):
• G-protein–linked receptors (GPCRs)—use heterotrimeric G proteins to relay signal.
• Protein-kinase–linked receptors—intrinsic or associated kinase activity (e.g., receptor tyrosine kinases).

Pharmacology: many drugs are agonists/antagonists for GPCRs or kinase receptors.
Pathology: defective amplification (e.g., insulin resistance) or aberrant integration (e.g., cancer signaling) leads to disease.
Therapeutic design leverages signal amplification—small-dose drugs can yield big physiological changes.