Q&A: Signaling Transduction

70 practice flashcards reviewing cellular signaling concepts, primary and secondary messengers, GPCRs, RTKs, Jak-STAT, TGF-beta/Smad pathways, and signal termination mechanisms.

What is the definition of cell signaling?

Complex cellular responses triggered by extracellular signals.

What cellular roles are regulated by signaling pathways according to the lecture?

Cellular differentiation and growth, cell division, cell motility, apoptosis, necrosis, senescence, neurotransmission, metabolic regulation, and muscle contraction.

What is step 1 in the sequence of events of a general signal-transduction pathway?

Release of primary signal (chemical messenger).

What is step 2 in the sequence of events of a general signal-transduction pathway?

Reception of signal by membrane receptors or intracellular diffusion.

What is step 3 in the sequence of events of a general signal-transduction pathway?

Conversion and amplification (transduction) of the signal by secondary messengers.

What is step 4 in the sequence of events of a general signal-transduction pathway?

Activation or inhibition of effectors to induce a physiological response.

What is step 5 in the sequence of events of a general signal-transduction pathway?

Termination of signal.

Which diagram illustrates the overall sequence from signal reception to transduction and physiological response?

Figure 13.01 depicting Signal $\rightarrow$ Reception $\rightarrow$ Amplification $\rightarrow$ Transduction $\rightarrow$ Response(s) with feedback loops.

What are the five main forms of cell signaling described in the lecture?

Endocrine, Paracrine, Synaptic, Autocrine, and Cell-cell contact (signaling by plasma-membrane-attached proteins).

What defines endocrine signaling?

Hormone secretion into the blood by an endocrine gland to act on distant target cells.

What defines paracrine signaling?

Secretion of chemical signals from a secretory cell into the extracellular space to act on adjacent target cells.

What defines autocrine signaling?

A cell releasing signals that bind to target receptors on the exact same cell.

How does signaling by plasma-membrane-attached proteins operate?

A signaling cell interacts directly with an adjacent target cell via cell-surface-attached membrane proteins.

Which diagram illustrates endocrine, paracrine, autocrine, and plasma-membrane-attached signaling mechanisms?

Figure 15-2 detailing the spatial modes of signaling communication.

What are primary chemical messenger examples in the nervous system?

Neurotransmitters (e.g., acetylcholine, epinephrine, GABA) and neuropeptides.

What polypeptide hormones and catecholamines act as endocrine primary signals?

Polypeptide hormones include insulin and glucagon; catecholamines include epinephrine.

What lipophilic or hydrophobic hormones serve as endocrine primary signals?

Thyroid hormones and steroid hormones (e.g., cortisol, aldosterone, sex hormones).

What primary signals function within the immune system?

Cytokines (e.g., interleukins, tumor necrosis factors, interferons) and chemokines.

What molecules belong to the eicosanoid class of primary signals?

Prostaglandins, thromboxanes, and leukotrienes.

What growth factors are listed as primary signals?

Epidermal growth factor (EGF) and platelet-derived growth factor (PDGF).

How do hydrophobic primary signals interact with target cells?

They diffuse across the plasma membrane and interact with cytosolic or nuclear intracellular receptors.

What function do hydrophobic ligand-receptor complexes perform inside the cell?

They function as transcription factors to induce gene expression.

Which diagram depicts small hydrophobic signals binding cytosolic or nuclear receptors?

The Intracellular Receptors diagram showing carrier protein delivery and gene expression regulation.

How do hydrophilic primary signals transmit their message into the cell?

They bind to cell-surface membrane receptors because they cannot cross the cell membrane.

In what two ways does ligand binding to a cell-surface receptor induce a signaling cascade?

By altering the catalytic or regulatory activity of the receptor, or by producing secondary messengers.

Which diagram illustrates hydrophilic signal molecules binding to cell-surface receptors?

The Cell-Surface Receptors diagram.

What three major classes of membrane receptors are outlined in the lecture?

Ion-channel receptors, G-protein coupled receptors (GPCRs), and kinase or kinase-binding receptors.

How do ion-channel receptors initiate signal transduction?

Through conformational changes induced by ligand binding.

What structural feature defines G-protein coupled receptors?

They are monomeric proteins with 7 transmembrane $\alpha$-helical domains.

What is another structural name given to G-protein coupled receptors?

Heptahelical receptors.

What are the roles of the GPCR N-terminus and C-terminus?

The extracellular N-terminus binds a specific ligand, while the intracellular C-terminus interacts with a heterotrimeric G-protein ($\alpha$, $\beta$, $\gamma$ subunits).

Which diagram shows the 7 transmembrane helices of a GPCR embedded in the plasma membrane?

The GPCR structure diagram depicting seven transmembrane helical domains.

What nucleotide is bound to the G$\alpha$ subunit in the resting (inactive) state?

Guanosine diphosphate ($\text{GDP}$).

What occurs upon ligand binding to a GPCR during G-protein activation?

Exchange of $\text{GDP}$ for $\text{GTP}$ and a conformational change in G$\alpha$.

What happens to the heterotrimeric G-protein complex after $\text{GTP}$ binds G$\alpha$?

G$\alpha$ affinity for the receptor and the $\beta\gamma$ subunits decreases, leading to complex dissociation.

Which components of an activated G-protein can interact with effector enzymes?

Either activated G$\alpha$ (bound to $\text{GTP}$) or released G$\beta\gamma$ subunits.

How is G-protein signaling terminated intrinsically?

The intrinsic GTPase activity of G$\alpha$ hydrolyzes $\text{GTP}$ to $\text{GDP}$, permitting reassociation of the heterotrimeric G-protein.

Which diagram illustrates the cycle of G-protein activation and inactivation?

The G-protein activation cycle diagram detailing ligand binding, $\text{GTP}$ exchange, effector interaction, and reassociation.

How many G$\alpha$, G$\beta$, and G$\gamma$ subunits exist in human cells?

Human cells contain 21 G$\alpha$ subunits (encoded by 16 genes), 6 G$\beta$ subunits, and 12 G$\gamma$ subunits.

Which G-protein subunits exhibit interchangeable activities?

The G$\beta\gamma$ subunits.

What effector, second messenger change, and receptors are associated with G$\alpha_s$?

Effector: Adenylyl cyclase; Second Messenger: Increased $\text{cAMP}$; Receptors: $\beta$-Adrenergic, glucagon, serotonin, and vasopressin receptors.

What effector, second messenger change, and receptors are associated with G$\alpha_i$?

Effector: Adenylyl cyclase and $\text{K}^+$ channel; Second Messenger: Decreased $\text{cAMP}$ and changed membrane potential; Receptors: $\alpha_2$-Adrenergic and muscarinic acetylcholine receptors.

What effector and second messenger response are associated with G$\alpha_{\text{olf}}$?

Effector: Adenylyl cyclase; Second Messenger: Increased $\text{cAMP}$ (in nose odorant receptors).

What effector, second messengers, and receptor example are associated with G$\alpha_q$?

Effector: Phospholipase C; Second Messengers: Increased $\text{IP}_3$ and $\text{DAG}$; Receptor: $\alpha_1$-Adrenergic receptor.

What effector and second messengers are associated with G$\alpha_o$?

Effector: Phospholipase C; Second Messengers: Increased $\text{IP}_3$ and $\text{DAG}$ (in endothelial acetylcholine receptors).

What effector, second messenger response, and receptor are associated with G$\alpha_t$ (Transducin)?

Effector: cGMP phosphodiesterase; Second Messenger: Decreased $\text{cGMP}$; Receptor: Rhodopsin in rod cells.

Which figure summarizes mammalian heterotrimeric G-protein classes, effectors, second messengers, and receptor examples?

Table 15-2 detailing major classes of mammalian heterotrimeric G proteins.

What is the primary function of secondary messengers?

To amplify the effects of extracellular signals within the cell.

What is the most common second messenger?

Cyclic AMP ($\text{cAMP}$).

What enzyme catalyzes $\text{cAMP}$ production from $\text{ATP}$?

Adenylyl cyclase.

What enzyme does $\text{cAMP}$ activate?

Protein Kinase A (PKA).

How is $\text{cAMP}$ signaling terminated?

By hydrolysis of $\text{cAMP}$ to $5'\text{-AMP}$ by $\text{cAMP}$ phosphodiesterases.

What is the subunit composition of inactive Protein Kinase A (PKA)?

It is a heterotetramer composed of 2 regulatory and 2 catalytic subunits ($\text{R}_2\text{C}_2$).

How many $\text{cAMP}$ molecules are required to activate one PKA complex?

4 molecules of $\text{cAMP}$.

What occurs when $\text{cAMP}$ binds to the regulatory subunits of PKA?

A conformational change occurs that releases and activates the 2 catalytic (C) subunits.

Which diagram shows the activation of PKA by $\text{cAMP}$ binding to regulatory subunits?

Figure 13.07 depicting $4\,\text{cAMP}$ binding regulatory subunits to release active catalytic subunits.

How does active PKA modulate gene expression?

By phosphorylating transcription factors, which induces or represses gene expression.

Which G-protein subunit class is involved in phosphoinositide signaling?

G$\alpha_q$ subunit.

What hormone examples signal via the phosphoinositide pathway?

Oxytocin, vasopressin, and angiotensin II.

Which enzyme cleaves $\text{PIP}_2$ in phosphoinositide signaling?

Phospholipase C (PLC).

What two secondary messengers are formed by the cleavage of $\text{PIP}_2$?

Diacylglycerol (DAG) and Inositol 1,4,5-trisphosphate ($\text{IP}_3$).

What is the location and target of Diacylglycerol (DAG)?

DAG remains anchored in the plasma membrane and activates Protein Kinase C (PKC).

What role does cytosolic $\text{Ca}^{2+}$ play in PKC activation?

High cytosolic $\text{Ca}^{2+}$ promotes the interaction between inactive PKC and membrane-bound DAG.

What is the location and target of Inositol 1,4,5-trisphosphate ($\text{IP}_3$)?

$\text{IP}_3$ diffuses into the cytosol and opens ligand-gated $\text{Ca}^{2+}$ channels in the endoplasmic reticulum (ER), releasing $\text{Ca}^{2+}$ into the cytoplasm.

How many cytosolic $\text{Ca}^{2+}$ ions bind to calmodulin to activate target protein kinases?

4 cytosolic $\text{Ca}^{2+}$ ions.

Which diagram shows calmodulin binding 4 calcium ions to form an active complex?

The Calmodulin activation diagram showing $\text{Ca}^{2+}$ binding, conformational change, and target protein interaction.

What structural features characterize Receptor Tyrosine Kinases (RTKs)?

RTKs are monomers with a single transmembrane $\alpha$-helix, an extracellular ligand-binding domain, and an intracellular domain with weak tyrosine kinase activity.

What is the mechanism of RTK activation following growth factor binding?

Ligand binds two RTK extracellular domains $\rightarrow$ homodimerization $\rightarrow$ cross-autophosphorylation of kinase domains $\rightarrow$ activation and phosphorylation of cytosolic tyrosine residues $\rightarrow$ creation of binding sites for adaptor proteins.

What defines Jak-STAT receptors prior to ligand binding?

They are monomeric receptors with no intrinsic kinase activity before binding Janus-like kinases (Jak).

What are the mechanisms of Jak-STAT, TGF-$\beta$/Smad pathways, and signal termination modes?

In Jak-STAT, cytokines dimerize receptors, activating Jak to cross-phosphorylate receptors and STATs; STATs dimerize and enter the nucleus. In TGF-$\beta$/Smad, TGF-$\beta$ binds Type II receptor to recruit/phosphorylate Type I, which phosphorylates Smad to form nuclear transcription complexes. Signal termination occurs rapidly (metabolic) or slowly (proliferative) via stimulus removal, $\text{GTP}$ hydrolysis (GTPases), second messenger degradation (phosphodiesterases), or dephosphorylation (phosphatases).