General Physiology - Chapter 5: Signal Transduction

Vocabulary flashcards covering General Physiology Chapter 5, including membrane receptors, G protein-coupled receptor pathways, second messengers (cAMP, IP3, DAG, Ca2+), eicosanoids, and signal transduction termination.

Ligand-Gated Ion Channel

A plasma membrane channel that undergoes a conformational change to form an open channel upon the binding of a specific first messenger (ligand).

Membrane Potential Change via Ligand-Gated Channels

An electrical response in the cell resulting from an increased net diffusion of specific ions across the plasma membrane following channel opening.

Common Ions Transported by Ligand-Gated Channels

$\text{Na}^+$, $\text{K}^+$, and $\text{Ca}^{2+}$

Receptors with Intrinsic Enzyme Activity

Receptors whose cytoplasmic portion functions directly as an enzyme, most commonly acting as protein kinases that phosphorylate specific amino acids.

Receptor Tyrosine Kinase (RTK)

A major class of membrane receptors with intrinsic enzyme activity that specifically phosphorylates tyrosine residues on cytoplasmic target proteins.

Autophosphorylation

The process in which an activated receptor tyrosine kinase phosphorylates its own cytoplasmic tyrosine groups upon ligand binding.

Phosphotyrosines

Phosphorylated tyrosine groups on the cytoplasmic portion of an activated receptor that serve as binding docking sites for intracellular proteins.

Primary Ligands for Receptor Tyrosine Kinases

Growth factors that influence cell proliferation and cellular differentiation.

Insulin Receptor

A specific example of a plasma membrane receptor that possesses intrinsic enzyme (tyrosine kinase) activity.

Receptors Interacting with Cytoplasmic Kinases

Receptors that lack intrinsic kinase activity and must bind and activate cytosolic protein kinases upon ligand-induced conformational change.

Janus Kinases (JAKs)

A family of four cytoplasmic tyrosine kinases that associate with specific membrane receptors and phosphorylate target proteins, including transcription factors.

JAK Kinase Pathway Outcome

The synthesis of new proteins inside the cell to mediate the cellular response to the first messenger.

Cytokines

Proteins secreted by cells of the immune system playing a critical role in immune defenses, which signal primarily via receptors linked to JAK kinases.

Heterotrimeric G Protein Subunits

The three distinct protein subunits—alpha ($\alpha$), beta ($\beta$), and gamma ($\gamma$)—that compose a G protein.

G Protein Alpha Subunit Binding

The functional subunit of a G protein that binds guanosine diphosphate ($\text{GDP}$) when inactive or guanosine triphosphate ($\text{GTP}$) when active.

G Protein Beta and Gamma Subunits

Subunits that function to anchor the alpha subunit of a G protein into the plasma membrane.

GPCR Conformational Change

Receptor activation upon ligand binding that increases the affinity of the G protein's alpha subunit for $\text{GTP}$.

G Protein Subunit Dissociation

The detachment of the $\text{GTP}$-bound alpha subunit from the beta and gamma subunits, enabling it to interact with effector proteins.

G Protein Effector Proteins

Plasma membrane targets—specifically ion channels or enzymes—activated or inhibited by an activated G protein alpha subunit.

Direct Ion Channel Regulation by G Proteins

Signal transduction in which an activated G protein subunit regulates an ion channel without the involvement of second messengers.

Indirect Ion Channel Regulation by G Proteins

Signal transduction in which a G protein regulates an ion channel through the production of intracellular second messengers.

Major G-Protein Regulated Effector Enzymes

Adenylyl cyclase and phospholipase C.

$G_s$ Protein

A stimulatory G protein that, upon activation, stimulates its effector protein adenylyl cyclase.

Adenylyl Cyclase

A membrane effector enzyme that catalyzes the conversion of cytosolic $\text{ATP}$ molecules into cyclic $\text{AMP}$ ($\text{cAMP}$).

Cyclic AMP (cAMP)

A key second messenger generated from cytosolic $\text{ATP}$ by the action of activated adenylyl cyclase.

cAMP-Dependent Protein Kinase (PKA)

An enzyme activated by binding $\text{cAMP}$ that subsequently phosphorylates target proteins on specific amino acids.

Triglyceride Breakdown in Adipocytes

A physiological process in fat cells stimulated by epinephrine acting via the $\text{cAMP}$ pathway to activate a phosphorylated lipase enzyme.

Adipose Response to cAMP Rise

Increase in hydrolysis of triglyceride and decrease in amino acid uptake.

Liver Response to cAMP Rise

Increase in conversion of glycogen to glucose, inhibition of glycogen synthesis, increase in amino acid uptake, and increase in gluconeogenesis.

Ovarian Follicle Response to cAMP Rise

Increase in synthesis of estrogen and progesterone in response to $\text{FSH}$ and $\text{LH}$.

Adrenal Cortex Response to cAMP Rise

Increase in synthesis of aldosterone and cortisol in response to $\text{ACTH}$.

Cardiac Muscle Response to cAMP Rise

Increase in heart muscle contraction rate in response to epinephrine.

Thyroid Gland Response to cAMP Rise

Secretion of thyroxine in response to thyroid-stimulating hormone ($\text{TSH}$).

Bone Tissue Response to cAMP Rise

Increase in resorption of calcium from bone in response to parathyroid hormone.

Skeletal Muscle Response to cAMP Rise

Conversion of stored glycogen to glucose in response to epinephrine.

Kidney Response to cAMP Rise

Increased resorption of water in response to vasopressin.

Blood Platelet Response to cAMP Rise

Inhibition of platelet aggregation and secretion in response to Prostaglandin I.

$G_i$ Protein

An inhibitory G protein that inhibits adenylyl cyclase, resulting in decreased cytosolic $\text{cAMP}$ generation and reduced protein phosphorylation.

Signal Amplification

A major cascade benefit of second messenger pathways where binding of 1 first messenger molecule can generate 1,000,000 phosphorylated final products.

Intrinsic GTPase Activity

An enzymatic activity inherent in the G protein alpha subunit that cleaves bound $\text{GTP}$ into $\text{GDP}$ plus $\text{P}_i$, returning the subunit to its inactive state.

cAMP Phosphodiesterase

The cytosolic enzyme that breaks down cyclic $\text{AMP}$ into inactive $\text{5'-AMP}$, terminating the $\text{cAMP}$ signal cascade.

Caffeine and Theophylline Mechanism

Widely consumed stimulants that inhibit phosphodiesterase activity, thereby prolonging the intracellular actions of $\text{cAMP}$.

Protein Phosphatases

Regulated enzymes that remove phosphate groups from phosphorylated proteins, effectively deactivating or altering target protein function.

$G_q$ Protein

A specific G protein class that couples receptor activation to the effector enzyme phospholipase C.

Phospholipase C (PLC)

A membrane-bound effector enzyme activated by $G_q$ that breaks down $\text{PIP}_2$ into the second messengers $\text{DAG}$ and $\text{IP}_3$.

Phosphatidylinositol Bisphosphate ($\text{PIP}_2$)

A plasma membrane phospholipid cleaved by activated phospholipase C to produce two distinct second messengers.

Diacylglycerol (DAG)

A lipophilic second messenger generated from $\text{PIP}_2$ cleavage that remains in the plasma membrane to activate protein kinase C.

Inositol Trisphosphate ($\text{IP}_3$)

A cytosolic second messenger generated from $\text{PIP}_2$ cleavage that binds to receptors on the endoplasmic reticulum to trigger $\text{Ca}^{2+}$ release.

Protein Kinase C (PKC)

An enzyme activated jointly by diacylglycerol ($\text{DAG}$) and cytosolic $\text{Ca}^{2+}$ that phosphorylates specific cell proteins to produce a cellular response.

Membrane-Bound Receptor Response Duration

Initiates a faster cellular response compared to lipid/steroid receptors, but produces a shorter, less sustained response.

Cytosolic Calcium Concentration Maintenance

Maintained at an extremely low concentration in the cytosol relative to extracellular fluid by active-transport pumps in the plasma membrane and organelle membranes.

Electrochemical Gradient for Calcium

A large concentration and electrical gradient favoring passive $\text{Ca}^{2+}$ influx into the cytosol upon the opening of membrane or ER $\text{Ca}^{2+}$ channels.

Calcium-Induced Calcium Release

A process where extracellular $\text{Ca}^{2+}$ entering through plasma membrane channels binds to $\text{Ca}^{2+}$-sensitive channels in the endoplasmic reticulum and opens them.

Calmodulin

An essential $\text{Ca}^{2+}$-binding protein present in virtually all cells that undergoes a conformational change upon binding calcium.

Calcium-Calmodulin Complex Functions

Activates or inhibits a wide variety of intracellular enzymes and proteins, particularly protein kinases, mediating the cell's response to stimuli.

Non-Calmodulin Calcium Target Proteins

Cytosolic proteins directly bound and activated by $\text{Ca}^{2+}$, including protein kinase C, troponin, nitric oxide synthase, and PY kinase.

Mechanisms Increasing Cytosolic Calcium

Opening of receptor-gated or voltage-gated plasma membrane $\text{Ca}^{2+}$ channels, $\text{IP}_3$-mediated release from ER, or inhibition of active $Ca^{2+}$ transport out of the cytosol.

Phospholipase A2 ($\text{PLA}_2$)

An enzyme activated by stimulus-receptor binding that splits arachidonic acid off from membrane phospholipids.

Arachidonic Acid (AA)

A membrane-derived fatty acid precursor that is metabolized into eicosanoids via cyclooxygenase or lipoxygenase pathways.

Cyclooxygenase Pathway

An enzymatic pathway converting arachidonic acid into cyclic endoperoxides, which yield prostaglandins, thromboxanes, and prostacyclin.

Lipoxygenase Pathway

An enzymatic pathway converting arachidonic acid into leukotrienes, which mediate allergic and inflammatory reactions.

Eicosanoids as Paracrine and Autocrine Agents

Molecules synthesized from arachidonic acid that are immediately released from cells to act locally before being rapidly metabolized by local enzymes.

NSAIDs Mechanism of Action

Nonsteroidal anti-inflammatory drugs (like aspirin and ibuprofen) that block cyclooxygenase, inhibiting prostaglandin and thromboxane synthesis.

Glucocorticoid Inhibition of Eicosanoids

Steroidal anti-inflammatory drugs (like cortisol) that block phospholipase $\text{A}_2$ activity, preventing arachidonic acid release.

Receptor Inactivation via Phosphorylation

A signal termination method where chemical alteration (phosphorylation) lowers receptor affinity for first messengers or blocks G protein coupling.

Receptor Endocytosis

A process of terminating signal transduction where plasma membrane receptors bound to first messengers are internalized into the cell.

Signal Transduction Cross-Talk

Interactions between different signaling pathways within a cell, where active molecules generated in one pathway modify receptors or signaling molecules in another.

First Messenger Concentration Reduction

The primary method to cease receptor activation, accomplished by extracellular enzymatic breakdown, reuptake by adjacent cells, or passive diffusion.