BILD1: Cell Signaling

Cell signaling

The process by which cells detect and respond to external signals through receptors and signaling pathways.

Reception

The stage of cell signaling where a signal molecule binds to a receptor protein.

Signal transduction

The stage of cell signaling where the receptor activates intracellular molecules to relay and amplify the signal.

Response

The final stage of cell signaling where the cell changes behavior or gene expression in response to a signal.

Ligand

A signaling molecule that binds specifically to a receptor.

Receptor protein

A protein that detects a signal molecule and initiates a cellular response.

Hydrophilic signal

A signal that cannot cross the membrane; its receptor is located on the cell surface.

Hydrophobic signal

A signal that can cross the membrane; its receptor is located inside the cell.

G protein-coupled receptor (GPCR)

A membrane receptor that activates a G protein when a ligand binds.

G protein

A molecular switch that binds GTP when active and GDP when inactive; transmits signals from GPCRs.

Receptor tyrosine kinase (RTK)

A receptor that phosphorylates itself and other proteins when activated by a ligand.

Ion channel receptor

A receptor that opens or closes an ion channel in response to ligand binding.

Second messenger

Small, nonprotein molecules (like cAMP or Ca²⁺) that relay signals inside the cell.

cAMP (cyclic AMP)

A common second messenger produced from ATP by adenylyl cyclase.

Adenylyl cyclase

An enzyme activated by a G protein that converts ATP to cAMP.

Protein kinase A (PKA)

A kinase enzyme activated by cAMP that phosphorylates target proteins.

Phosphorylation

Addition of a phosphate group to a molecule, often activating or deactivating a protein.

Dephosphorylation

Removal of a phosphate group by a phosphatase enzyme.

Phosphatase

An enzyme that removes phosphate groups, turning off signaling pathways.

Signal amplification

One ligand can trigger activation of many downstream molecules, multiplying the signal.

Feedback regulation

Process where the output of a pathway regulates its own activity.

Insulin

A protein hormone secreted by the pancreas that lowers blood glucose by stimulating glucose uptake.

Insulin receptor

A receptor tyrosine kinase that binds insulin and triggers glucose uptake in cells.

GLUT4 transporter

A glucose transporter that moves to the plasma membrane in response to insulin signaling.

IRS protein (insulin receptor substrate)

A signaling protein phosphorylated by the insulin receptor that activates PI3K.

PI3K enzyme

Activated by IRS; generates lipid signals that activate Akt.

Akt protein kinase

Activated by PI3K; triggers GLUT4 transporters to move to the membrane for glucose uptake.

Reception in insulin signaling

Insulin binds to the receptor, activating its kinase activity.

Signal transduction in insulin signaling

Receptor autophosphorylates → IRS phosphorylated → PI3K → Akt activated.

Response in insulin signaling

GLUT4 moves to membrane → glucose enters cell → blood sugar decreases.

Type 2 diabetes

A disorder where cells become resistant to insulin and fail to take up glucose properly.

Insulin resistance

Condition where signaling after insulin receptor activation is impaired.

Effect of IRS phosphorylation defect

PI3K and Akt activation are reduced → GLUT4 fails to move → less glucose uptake.

Effect of constitutively active insulin receptor

Receptor always on → excess glucose uptake → low blood sugar.

Phosphatase inhibitors in diabetes

Inhibit enzymes that remove phosphates, keeping insulin pathway active longer to increase glucose uptake.

Epinephrine (adrenaline)

A hydrophilic hormone that triggers the fight-or-flight response.

Epinephrine receptor

A GPCR on the surface of target cells that binds epinephrine.

Fight-or-flight response

A rapid physiological reaction that increases heart rate, blood sugar, and energy availability.

Glycogen breakdown

Epinephrine signaling activates enzymes that break glycogen into glucose for energy.

cAMP in epinephrine signaling

Acts as a second messenger to activate PKA, which then activates enzymes for glycogen breakdown.

Signal amplification in epinephrine pathway

One epinephrine molecule → many cAMP → many PKA → massive glucose release.

Phosphodiesterase

Enzyme that breaks down cAMP, turning off the signal.

Overactive phosphodiesterase

Reduces cAMP levels → less PKA activation → decreased glucose release.

Caffeine effect on signaling

Inhibits phosphodiesterase → higher cAMP → prolonged PKA activation → more energy and alertness.

Hydrophilic vs hydrophobic signal receptors

Hydrophilic signals bind membrane receptors; hydrophobic signals bind intracellular receptors.

Steroid hormone receptor

Intracellular receptor that binds hydrophobic hormones (e.g., testosterone) and regulates gene expression.

Testosterone receptor

A hydrophobic hormone receptor found inside target cells that acts as a transcription factor.

Specificity of response

Different cells can respond differently to the same signal due to different receptor types or pathways.

Cross-talk

Interaction between signaling pathways that fine-tunes the overall cellular response.

Desensitization

Reduction in cell response after prolonged exposure to a signal, often by receptor internalization.

Signal termination

Occurs when ligand dissociates, GTP is hydrolyzed, cAMP is degraded, and phosphatases remove phosphates.

Mutation in GPCR that cannot bind GTP

G protein cannot activate → no signal transduction → no cellular response.

Mutation preventing GTP hydrolysis in G protein

G protein stays active → prolonged signal → possible overstimulation.

Amplification importance

Ensures that small hormone amounts can produce large, fast responses during stress.

Cell-surface receptor

Receptor located on the plasma membrane that binds hydrophilic ligands.

Intracellular receptor

Receptor inside the cell that binds hydrophobic ligands such as steroids.

Second messenger cascade

Series of intracellular reactions where each step activates multiple downstream molecules.

Kinase cascade

A signaling sequence where one kinase activates another, resulting in amplification.

Selectivity of signaling

Determined by receptor type, ligand, and downstream effectors in the cell.

Mutation blocking receptor phosphorylation

Stops signal transduction even if ligand is bound.

Receptor overexpression

Leads to excessive signaling even with low ligand concentration.

Feedback inhibition

Cell reduces receptor activity or signal strength when output is high.

Desensitized receptor

Receptor becomes less responsive to a ligand after continuous exposure.