Cell Biology- Chapter 16

Signal Transduction

Conversion of information to different forms.

Cell Communication Distances

Cells communicate over variable distances: paracrine, neuronal, contact-dependent, endocrine.

Paracrine Signaling

• Local mediators diffuse through extracellular fluid to nearby target cells.

• Important in inflammation and tissue repair.

Neuronal Signaling

• Synaptic transmission via neurotransmitters.

• Occurs between neurons or neurons and muscle cells.

Contact-Dependent Signaling

• Requires direct cell-to-cell contact.

• Important in development and immune response.

Endocrine Signaling

• Hormones travel through bloodstream to distant targets.

• Regulates metabolism, growth, reproduction.

Receptor Location Based on Signal Molecule

• Polar molecules: cell surface receptors.

• Hydrophobic molecules: intracellular receptors (act as transcription factors).

A Single Signal Molecule Can Have Multiple Effects

Example: Acetylcholine affects different tissues differently.

Signal Integration and Apoptosis

• Absence of signals can lead to apoptosis (e.g., anoikis from detachment).

Fast vs. Slow Signal Responses

• Fast: Existing protein modifications.

• Slow: Gene expression changes

Signal Pathway Branching

• A single pathway can relay signals to multiple targets.

Signal Pathway Convergence

• Different pathways activating the same intracellular signaling molecule.

Positive and Negative Feedback in Signaling

• Positive: Enhances upstream activity.

• Negative: Inhibits upstream activity (can create oscillations).

Molecular Switches: Phosphorylation and GTP Binding

• Kinase/phosphatase activity regulates phosphorylation.

• GTP binding proteins switch between active/inactive states.

Monomeric (Small) GTPases Regulation

• GEFs (guanine nucleotide exchange factors) activate.

• GAPs (GTPase-activating proteins) inactivate.

G Protein Function and Mutations

• GTP binding, not hydrolysis, activates G proteins.

• Ras mutations (defective GTP hydrolysis) drive cancer.

Ion Channel-Coupled Receptors

• Open/close upon ligand binding.

• Directly alter membrane potential (ionotropic signaling).

G Protein-Coupled Receptors (GPCRs)

• Trimeric G proteins activated upon ligand binding.

• Initiate intracellular signaling cascades.

GPCR Activation Mechanism

• Ligand binding alters receptor conformation.

• GTP replaces GDP in the alpha subunit, triggering dissociation.

GTP Hydrolysis and G Protein Inactivation

• Alpha subunit hydrolyzes GTP to GDP.

• Reassociates with beta-gamma complex.

G Protein Subunit Functions

Alpha and beta-gamma subunits can each signal independently.

Second Messengers in GPCR Signaling

• cAMP, IP3, DAG, Ca++ amplify and relay signals.

Gas and Gai Regulation of cAMP

• Gas activates adenylyl cyclase (increases cAMP).

• Gai inhibits adenylyl cyclase (decreases cAMP).

Protein Kinase A (PKA) Activation by cAMP

• PKA phosphorylates cytoplasmic and nuclear targets.

GPCR Control of Heart Rate

• Parasympathetic: Acetylcholine decreases heart rate.

• Sympathetic: Norepinephrine increases heart rate.

Cholera and Pertussis Toxins Affecting cAMP

• Cholera: Locks Gas active → excessive cAMP → diarrhea.

• Pertussis: Inhibits Gai → excessive cAMP → immune suppression.

Gq Signaling via Phospholipase C (PLC)

• PLC cleaves PIP2 → IP3 & DAG.

• IP3 releases Ca++, DAG activates PKC

Ras and Receptor Tyrosine Kinases (RTKs)

• RTK activation leads to Ras activation via Ras-GEF.

• Ras initiates MAP kinase cascade → cell proliferation.

PI3K/Akt Pathway and Cell Survival

• PI3K converts PIP2 to PIP3 → Akt activation.

• Akt inhibits apoptosis by phosphorylating Bad.

mTOR Pathway in Cell Growth

• Akt activates mTOR → protein synthesis, cell growth.

• Inhibited by rapamycin (extends lifespan).