Lodish Ch 15.1-2 TB MC

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Questions and Answers

In paracrine signaling, the signaling molecule:

  • acts on cells in close proximity to the secreting cell. (correct)
  • is carried to the target cells via the circulation.
  • acts on target cells far away from the secreting cell.
  • acts on the same cells that secreted the signaling molecule.

GTPases serve in many signal transduction pathways and the presence of GTP or GDP dictates whether the pathway is on or off, respectively. Which of the following statements is TRUE regarding guanine nucleotide exchange factors (GEF) and the role in these signaling pathways?

  • They hydrolyze GTP into GDP and Pi.
  • They decrease the GTPase activity of the G-protein.
  • They catalyze the dissociation of GDP on the G-protein and promote the replacement of GTP. (correct)
  • none of the above

Cell sensitivity to an external signal is determined by:

  • the number of surface receptors. (correct)
  • koff.
  • kon.
  • Kd.

If [R] = the free receptor concentration and [L] = the free ligand concentration, Ka is:

<p>[R][L]/[RL]. (A)</p> Signup and view all the answers

Pull-down assays using proteins that ONLY bind to the GTP-bound version of the small G-protein can be used to detect when small G proteins like Rac1 have been activated by various growth factors. You were given two lysates, one having been treated with platelet-derived growth factor (PDGF) and the other not treated with PDGF. This method is similar to performing co-IPs, so based on that knowledge, which of the following steps is erroneous?

<p>The tubes are vortexed well, loading buffer is added, and the samples are heated to aid in protein denaturation. (D)</p> Signup and view all the answers

Of the components of a heterotrimeric G protein, which subunit(s) is(are) able to activate downstream responses?

<p>both the alpha subunit and the beta/gamma subunits (C)</p> Signup and view all the answers

In trimeric G proteins, GTP binds to:

<p>the a subunit. (C)</p> Signup and view all the answers

Which of the following is NOT a common intracellular second messenger?

<p>adenosine triphosphate (ATP) (A)</p> Signup and view all the answers

Phospholipase C is activated by:

<p>Gaq. (C)</p> Signup and view all the answers

Which of the following general statement(s) about a G protein-coupled receptor is (are) TRUE?

<p>It is positioned with the C-terminus on the cytoplasmic face of the membrane. (C)</p> Signup and view all the answers

All the following statement(s) about cholera toxin are TRUE, except:

<p>it is a G protein-coupled receptor. (D)</p> Signup and view all the answers

Phosphatidylinositol 4,5-bisphosphate (PIP2) is cleaved by phospholipase C into:

<p>1,2-diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). (C)</p> Signup and view all the answers

1,2-diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) are cleaved from phosphatidylinositol 4,5-bisphosphate (PIP2) by the enzyme:

<p>phospholipase C. (A)</p> Signup and view all the answers

CGMP phosphodiesterase catalyzes the conversion of:

<p>cGMP to 5'-GMP. (A)</p> Signup and view all the answers

Which enzyme plays a role in regulating rhodopsin-induced closing of cation channels?

<p>phosphodiesterase (D)</p> Signup and view all the answers

Which of the following is a common step in the opening/closing of ion channels by acetylcholine and rhodopsin binding to their receptors?

<p>The Ga GTP subunit dissociates from the Gẞy complex. (C)</p> Signup and view all the answers

Rhodopsin, a light-sensitive GPCR whose role in vision is dependent on its phosphorylation status, is influenced in part by the protein arrestin. Which of the following is TRUE with regard to rhodopsin and vision?

<p>Arrestin binds to the completely phosphorylated opsin to inhibit signaling. (B)</p> Signup and view all the answers

The G protein stimulated by light via the Rhodopsin receptor is ______ , while the effector is ______

<p>Gat; PDE (C)</p> Signup and view all the answers

Which of the following statements about adenylyl cyclase stimulation/inhibition in adipose cells is TRUE?

<p>Epinephrine stimulates adenylyl cyclase. (A)</p> Signup and view all the answers

Which of the following events occur during the epinephrine-stimulated conversion of glycogen to glucose-1-phosphate?

<p>all of the above (D)</p> Signup and view all the answers

The activity of ẞ-adrenergic receptors is regulated by:

<p>ẞ-adrenergic receptor kinase (BARK). (A)</p> Signup and view all the answers

Which of the following mechanisms can terminate an intracellular signaling pathway once the concentration of an external signal decreases?

<p>all of the above (D)</p> Signup and view all the answers

When the regulatory domain of PKA is bound to cAMP:

<p>the released catalytic subunit travels to the nucleus where it can phosphorylate CREB. (B)</p> Signup and view all the answers

Muscarinic acetylcholine receptors are GPCRs that slow the rate of heart muscle contraction upon ligand binding/activation. Activation of this receptor leads to opening of potassium channels triggered by decreases in cAMP levels. The muscarinic acetylcholine receptor likely couples to:

<p>Gai. (B)</p> Signup and view all the answers

Cholera toxin can make you sick through overactivation of a Gαs pathway even if your body stops making the ligand associated with activation of the pathway. Knowing this , which of the following CANNOT be true about cholera toxin?

<p>Cholera toxin activates a ligand-activated G protein-coupled receptor. (B)</p> Signup and view all the answers

Signal amplification is an important part of GPCR-mediated signaling. Which of the following steps do NOT directly amplify the signal?

<p>binding of second messenger to target protein/ion channel (C)</p> Signup and view all the answers

One form of receptor desensitization can be mediated by negative feedback involving phosphorylation of the receptor itself by a kinase activated downstream of a second messenger. The phosphorylated receptor likely:

<p>could be resistant to desensitization if Ser/Thr phosphatases were acting on the same receptor. (B)</p> Signup and view all the answers

Which type of experimental evidence shows that the intrinsic GTPase activity of the Gα subunit is important for terminating effector activation?

<p>A nonhydrolyzable GTP analog that can bind to the Gα subunit but cannot be hydrolyzed by the intrinsic GTPase, thereby activating the effector protein longer upon ligand-induced activation of the receptor. (C)</p> Signup and view all the answers

Flashcards

Paracrine Signaling

Signaling where molecules act on cells near the secreting cell.

Guanine Nucleotide Exchange Factor (GEF)

Enzyme that promotes GTP binding to G protein, turning it 'on'.

Endocrine Signaling

Signaling using molecules carried through the circulatory system.

Autocrine Signaling

Signaling where molecule effects the cell that produced it.

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Kd

Dissociation constant; measure of ligand-receptor binding strength.

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Agonist

Molecule that mimics natural ligand, causing a response.

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Antagonist

Molecule that blocks receptor, preventing normal response.

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Trimeric G protein

G protein with alpha, beta, and gamma subunits.

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IP3 (inositol trisphosphate)

Second messenger; triggers calcium release.

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DAG (diacylglycerol)

Second messenger; activates protein kinase C.

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Rhodopsin

Light-sensitive GPCR in vision.

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Arrestin

Protein that inhibits rhodopsin signaling.

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cGMP phosphodiesterase

Enzyme that converts cGMP to GMP.

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PKA

Protein kinase A, activated by cAMP.

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Study Notes

Signal Transduction and G-Protein Coupled Receptors

  • Paracrine signaling involves signaling molecules acting on cells close to the secreting cell.
  • Guanine nucleotide exchange factors (GEFs) catalyze the dissociation of GDP on the G-protein and promote the replacement of GTP.
  • Endocrine signaling releases signaling molecules into the bloodstream to affect distant target cells.
  • Paracrine signaling involves signaling molecules affecting nearby target cells.
  • Autocrine signaling affects the signaling cell itself along with target cells.
  • Cell sensitivity to external signals is determined by the number of surface receptors.
  • Ka is calculated as [R][L]/[RL], where [R] is free receptor concentration, [L] is free ligand concentration and [RL] is receptor-ligand complex.
  • Agonists mimic natural ligands to initiate normal responses, while antagonists bind to receptors but don't induce a response, blocking natural ligand binding.
  • G protein-coupled receptors have functional domains identified via chimeric receptor experiments.
  • Pull-down assays detect activated small G proteins like Rac1, by binding the GTP-bound form to beads and then analyzing the resulting proteins.

GTPase Switch Proteins

  • GTPase switch proteins cycle between active (GTP-bound) and inactive (GDP-bound) states with GEF promoting GTP binding and intrinsic GTPase activity causing GTP hydrolysis back to GDP.

cAMP Phosphodiesterase

  • cGMP phosphodiesterase converts cGMP to 5'-GMP.

Signal Amplification and Termination

  • Signal amplification is a key aspect of G protein-coupled receptor (GPCR) signaling.
  • Signal termination mechanisms include receptor desensitization, second messenger degradation, and deactivation of signal transduction proteins.
  • Intrinsic GTPase activity of the α subunit of a G protein is crucial for terminating effector activation.

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