Signal Transduction Overview

Signal Transduction Overview

• Extracellular signals are converted into intracellular signals.
• A signaling molecule (ligand) binds to a specific receptor on the target cell.

Signaling Cascade

• The binding of a ligand to a receptor activates a cascade of intracellular enzymes and molecules (second messengers).
• This cascade leads to a specific cellular response.
• Signal amplification increases the number of signaling molecules at each step of the cascade.

Receptor Types

• Cell surface receptors (membrane receptors): Located in the cell membrane.
• Intracellular receptors: Located inside the cell.
• Nuclear receptors: A type of intracellular receptor that acts inside the nucleus.

Extracellular Messengers

• Lipophilic messengers: Can pass through the cell membrane to bind to intracellular receptors.
• Hydrophilic messengers: Cannot pass through the membrane and act on membrane receptors to initiate a signal.

Intracellular Receptors

• Lipophilic hormones diffuse through the cell membrane.
• Hormones bind to receptors, forming a complex.
• The hormone-receptor complex binds to hormone-responsive elements.
• This leads to changes in gene expression.

Cell Surface Receptors

• Three types:
  • G protein-coupled receptors
  • Enzyme-linked receptors
  • Ligand-gated ion channels

G Protein-Coupled Receptors (GPCRs)

• Seven transmembrane helices
• Binding sites for ligands in extracellular regions
• Intracellular binding site for G protein
• Ligand binding causes a conformational change in the receptor.
• Activated G protein binds GTP and dissociates.
• GTPase hydrolyzes GTP to GDP, resetting the G protein.
• Different G protein types interact with different effector molecules.

G Protein Subunits

• α subunit, binds GDP (inactive) and GTP (active state).
• β and γ subunits, stable complex with lipid anchor in the membrane.

G Protein Functions

• Gs proteins stimulate adenylyl cyclase.
• Gi proteins inhibit adenylyl cyclase.
• Gq proteins stimulate phospholipase C.

Receptor Tyrosine Kinases (RTKs)

• Extracellular domain
• Single transmembrane domain
• Intracellular domain with tyrosine kinase activity
• Ligand binding triggers dimerization and autophosphorylation of cytoplasmic tyrosine residues.
• This initiates downstream signaling cascades.

Non-receptor Tyrosine Kinases and Activation

• Membrane receptors without tyrosine kinase activity.
• Ligand binding causes receptor dimerization.
• JAK proteins phosphorylate each other.
• This initiates STAT protein activation.
• STAT dimers effect gene expression in the nucleus.

Ligand-Gated Ion Channels

• Ligand binding induces a conformational change.
• Pore opening allows ion movement across the membrane.
• Altered membrane potential leads to rapid response.

Second Messengers

• Small molecules that mediate intracellular response to extracellular stimuli.
• Examples: cAMP, cGMP, IP3, Ca2+

Cyclic AMP (cAMP)

• Synthesized from ATP by adenylyl cyclase
• Gs proteins activate adenylyl cyclase.
• Gi proteins inhibit adenylyl cyclase.
• cAMP is degraded by phosphodiesterase to AMP.

Cyclic GMP (cGMP)

• Synthesized from GTP by guanylyl cyclase.
• Activates cGMP-dependent protein kinase G.
• Mediates smooth muscle relaxation.
• Degraded by phosphodiesterase.
• PDE inhibitors used in treating pulmonary hypertension and erectile dysfunction.

Nitric Oxide (NO)

• Short half-life, diffuses across membranes.
• Synthesized in endothelial cells of blood vessels.
• Activates guanylyl cyclase, increasing cGMP and leading to vascular relaxation.

Inositol Trisphosphate (IP3)

• Second messenger released by phospholipase C's action on membrane phospholipids.
• Causes release of Calcium from the endoplasmic reticulum, raising intracellular Calcium concentration.
• This triggers smooth muscle contraction.

Calcium (Ca2+) as a Second Messenger

• Intracellular Ca2+ levels are usually low.
• Second messengers or action potentials raise Ca2+ levels, triggering various cellular responses.

This quiz covers the fundamentals of signal transduction, focusing on how extracellular signals are transformed into intracellular responses. It includes details about signaling cascades, receptor types, and different categories of extracellular messengers. Test your understanding of these essential biological processes.