Cellular Signaling and cAMP Regulation

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Questions and Answers

What role does cAMP-phosphodiesterase play in cellular signaling?

It synthesizes cAMP.

It activates Protein Kinase A.

It cleaves cAMP, making it short-lived. (correct)

It increases levels of phospholipase C.

What initiates the protein phosphorylation cascade in many signaling pathways?

Dephosphorylation by kinases.

Inhibition from calcium ions.

Phosphorylation by kinases. (correct)

Phosphorylation by phosphatases.

Which of the following is NOT a target of Protein Kinase A in cAMP regulated pathways?

Heart rate regulation in the cardiovascular system.

Water reabsorption in the kidney.

Glycogen breakdown in the liver.

Calcium channel activation in muscle. (correct)

What are the two second messengers produced by the action of phospholipase C?

Inositol-1,4,5-Trisphosphate and DAG. Signup and view all the answers

What is the effect of DAG in cellular signaling?

Activates Protein Kinase C. Signup and view all the answers

What is one primary purpose of cell-cell communication in multicellular organisms?

To enable coordinated function of cells Signup and view all the answers

Which type of signaling involves messenger molecules that travel only short distances?

Paracrine signaling Signup and view all the answers

Which type of receptor is directly involved in the cAMP signaling pathway?

Trimeric G-Protein coupled receptors Signup and view all the answers

What role does nitric oxide play in cell signaling?

It functions as a local signaling molecule Signup and view all the answers

Which of the following is NOT a characteristic of hormones in long-distance signaling?

They require direct cell contact Signup and view all the answers

What is a primary function of ion channels in cell signaling?

They facilitate membrane depolarization Signup and view all the answers

What is the significance of cell junctions in local signaling?

They allow for direct cytoplasmic connection between adjacent cells. Signup and view all the answers

What pathway is activated by Tyrosine Kinase receptors?

MAP Kinase Cascade Signup and view all the answers

What is a ligand?

A molecule that binds to a specific site on another molecule Signup and view all the answers

Which type of receptor is most common in cell signaling?

Enzyme-linked receptors Signup and view all the answers

What is the purpose of the transduction cascade in cell signaling?

To relay and amplify the signal inside the cell Signup and view all the answers

Which of the following is an example of a small biomolecule that can act as a signal?

ATP (adenosine tri-phosphate) Signup and view all the answers

What type of cellular response is influenced by altered gene expression during signal transduction?

Modified cell shape Signup and view all the answers

Which component serves as the initial sensor in the signal transduction pathway?

Receptor Signup and view all the answers

What role do relay molecules play in a signal transduction pathway?

To amplify and propagate the signal Signup and view all the answers

Which of the following does NOT represent a type of signaling molecule?

Structural proteins Signup and view all the answers

What is the role of receptor tyrosine kinases in cellular signaling?

They act as enzymes to phosphorylate proteins. Signup and view all the answers

What happens to receptor tyrosine kinases upon binding with a signal molecule?

They dimerize and activate. Signup and view all the answers

How do ion channel receptors change to allow ions to pass through?

They change shape in response to a ligand. Signup and view all the answers

Which of the following ions can pass through ligand-gated ion channel receptors?

Na+ or Ca2+ ions. Signup and view all the answers

What is the end result of receptor tyrosine kinase signaling?

Stimulation of cellular response. Signup and view all the answers

What is the state of a receptor tyrosine kinase before it is activated?

Inactive monomer. Signup and view all the answers

What role does the Na+/K+ ATPase play in relation to ion channels?

It maintains the electrochemical gradient. Signup and view all the answers

Which statement best describes the function of ligand-gated ion channels?

They open upon ligand binding to allow ion flow. Signup and view all the answers

How many tyrosine residues are typically involved in receptor tyrosine kinase activity as indicated in the diagram?

Six tyrosines. Signup and view all the answers

What is a common property of both receptor tyrosine kinases and ion channel receptors?

They both remain inactive until ligands bind. Signup and view all the answers

What happens to a receptor when signal molecules leave it?

It reverts to its inactive state. Signup and view all the answers

What effect does cholera toxin have on the Gs protein?

It modifies the protein to stay constantly active. Signup and view all the answers

Which of the following is a mechanism for terminating a signaling cascade?

Hydrolysis of GTP. Signup and view all the answers

What characterizes proto-oncogenes in the context of cell signaling?

They are proteins promoting cellular transformation. Signup and view all the answers

What is a common characteristic of oncogenes associated with cancer?

They are often viral protein kinases that are constitutively active. Signup and view all the answers

How do beta blockers function at a molecular level?

They block the shape of neurotransmitters from binding to receptors. Signup and view all the answers

What is the role of cyclic AMP in cell signaling?

It acts as a secondary messenger to activate target enzymes. Signup and view all the answers

Which of the following is NOT a common target for cancer drug therapies mentioned?

Atorvastatin Signup and view all the answers

What is the primary function of receptor-associated binding proteins like the c-ras family?

They act as signaling proteins. Signup and view all the answers

What role does cAMP play in cellular signaling pathways?

It operates as a second messenger. Signup and view all the answers

What occurs during the amplification event in signal transduction?

A small amount of ligand causes a large response. Signup and view all the answers

What happens when epinephrine binds to a G-protein-linked receptor?

An active G protein is generated. Signup and view all the answers

What does protein kinase A (PKA) phosphorylate?

Downstream target enzymes. Signup and view all the answers

Which molecule is responsible for the amplification of the signal cascade in this pathway?

Cyclic AMP. Signup and view all the answers

What is the end product of activated glycogen phosphorylase?

Glucose-1-phosphate. Signup and view all the answers

What initiates the signal transduction cascade described in the content?

Binding of epinephrine to the receptor. Signup and view all the answers

How does protein phosphorylation affect enzymes in this signaling pathway?

It can either activate or deactivate them. Signup and view all the answers

What is the function of phosphorylase kinase in this pathway?

To activate glycogen phosphorylase. Signup and view all the answers

What is the final result of the activation cascade involving glucose metabolism?

Increased production of glucose-1-phosphate. Signup and view all the answers

How is the GTP-bound G protein inactivated after the signaling process?

By hydrolysis of GTP to GDP. Signup and view all the answers

Which process is not a part of signal amplification in this pathway?

Phosphorylation of a single target enzyme. Signup and view all the answers

What does the release of glucose-1-phosphate from glycogen primarily lead to?

Immediate energy usage by cells. Signup and view all the answers

Study Notes

Cell-Cell Communication

Cells need to communicate to proliferate, differentiate, migrate, and maintain a functional state.
Cell-cell signaling coordinates cellular function within and between tissues, up to the organism level.
Signaling informs cells about their identity, location, and assigned roles.
External signals are converted into internal responses. Prokaryotes respond mostly to chemical signals, while humans respond to various cues like light, sound, and chemicals in food.
Communication occurs via direct contact or chemical signals.

Local and Long-Distance Signaling

Multicellular organisms use chemical messengers for communication.
Animal and plant cells communicate directly via cell junctions.
In local signaling, animal cells may communicate via direct contact.
Animal cells also use local regulators (messenger molecules) for short-distance signaling.
For long-distance signaling, plants and animals use hormones.

Signals act over different ranges

Endocrine signaling uses hormones to travel through the bloodstream to distant target cells (e.g., estrogen, epinephrine).
Paracrine signaling involves local regulators acting on nearby cells (e.g., nitric oxide, histamine, prostaglandins).
Neuronal/synaptic signaling involves neurotransmitters released across synapses to target cells (e.g., neurotransmitters).

Signal Transduction Pathway

Extracellular signals are received by receptors on the cell surface.
Intracellular signaling pathways convert the signal into a cellular response.
A signal receptor (sensor), transduction cascade, targets, and the overall response are crucial parts of the pathway.
The response can change metabolic activity, gene expression, and cytoskeletal protein function, influencing cell shape or motility.

Signal

Signal = ligand; a molecule that binds to a specific receptor site on a protein.
Ligands include peptides/proteins (growth factors), amino acid derivatives (e.g., epinephrine, histamine), small biomolecules (ATP, steroids, prostaglandins), gases (nitric oxide), photons, and damaged DNA.

Receptors

Receptors sense and initiate signal transduction.
Extracellular receptors (cell surface receptors) are common in enzyme-linked receptors, exemplified by growth factor receptors.
Intracellular receptors (steroid receptors) reside inside the cell, typically for small/hydrophobic chemical transmitters.

Intracellular Receptors

Some receptor proteins are intracellular, situated in the cytosol or nucleus of target cells.
Small or hydrophobic chemical messengers easily cross the cell membrane and activate receptors.
Steroid and thyroid hormones are examples of hydrophobic messengers.
Activated hormone-receptor complexes act as transcription factors, modifying gene expression.

3 Types of Extracellular Cell-surface Receptors

Ion channel-linked receptors act as gates, allowing specific ions (e.g., Na+, Ca2+) to pass when a ligand binds.
Trimeric G protein-linked receptors act as on/off switches. GDP binding inactivates the G protein. GTP binding activates it.
Enzyme-linked receptors (tyrosine kinase) are membrane-bound receptors that phosphorylate target molecules upon ligand binding.

Trimeric G protein-linked receptors

A G protein-coupled receptor (GPCR) is a type of plasma membrane receptor that works with the help of a G protein.
The G protein acts as an on/off switch. If GDP is bound to the G protein, the G protein is inactive.

G-protein activation

Ligand binding triggers GDP-GTP exchange, causing the G protein to become active.
The alpha subunit dissociates from the beta-gamma complex.
The active G protein subunits alter the activity of effector enzymes.

All G proteins are similar in structure/activation.

Two primary classes of pathways:
- Adenylyl cyclase pathway
- Phospholipase C pathway

An Activated G\o-Protein-GTP

An activated G protein activates adenylyl cyclase to produce cyclic AMP (cAMP), a second messenger.
cAMP activates protein kinase A (PKA).
Various cellular responses are ultimately initiated.

Protein Kinase A

Protein kinase A (PKA) phosphorylates downstream target enzymes, typically by adding a phosphate group to them.
This phosphorylation typically alters enzyme activity, leading to the desired cellular response.

A Signal Cascade (Amplification)

Binding of epinephrine to a receptor sets off a cascade of events.
Each step causes a significant increase in number of molecules, leading to a amplified response.

Protein Phosphorylation and Dephosphorylation

Many pathways for signal transmission involve a cascade of protein phosphorylations.
Protein phosphatases remove phosphate groups to deactivate enzymes, allowing a switch in activity.

What are targets for Protein Kinase A?

Various pathways regulated by cAMP.
Glycogen breakdown: Targets include muscle, liver.
Heart rate: Targets are cardiovascular, kidney.
Water reabsorption: Targets are kidney.

Target protein Phospholipase C

The target effector enzyme in this pathway is phospholipase C (PLC).
PLC cleaves the membrane phospholipid, phosphatidylinositol (PIP\2) into two second messengers: inositol-1, 4, 5-trisphosphate (InsP3), and diacylglycerol (DAG).

Calcium Signaling

DAG activates protein kinase C, which alters cellular responses.
InsP3 acts as a second messenger to trigger the release of Ca2+ from intracellular stores.
Calcium ions participate in various cellular events, such as smooth muscle contraction

Receptor Tyrosine Kinases

Receptor tyrosine kinases (RTKs) are cell surface receptors.
Upon ligand binding, RTKs dimerize and cross-phosphorylate their cytoplasmic tyrosine residues.
Phosphorylated tyrosines serve as docking sites for signaling proteins, leading to cellular responses.
An example is the insulin receptor.

Receptors for everything

Receptors fit into specific shapes (lock-and-key model), a key feature of receptor specificity.

Proto-oncogenes- Signaling Proteins

Proto-oncogenes are proteins that promote cell transformation.
Many oncogenes are viral protein kinases that are constitutively active.
Examples include Serine-Threonine (like c-raf, ERK, akt) and Tyr kinases (like src, abl).

Activation of Epidermal Growth Factor Receptor by Mutation

Some receptors can activate even in the absence of a ligand, due to mutation.
The v-erbB of AEV lacks the C-terminal domains necessary for regulation.
Such mutations play a role in human breast cancer.

Cancer Drug-targeting therapy

The strategy targets areas inside the signaling pathway to block the spread of cancer cells.

Termination of the Signal

Inactivation mechanisms are crucial for controlling and terminating signaling pathways.
When signal molecules leave the receptor, the receptor returns to an inactive state.

Intracellular Signaling & Diseases

Cholera is an example of a disruption of a signal transduction pathway.
Vibrio cholerae produces an enterotoxin that modifies Gs, preventing proper deactivation of the system, leading to severe fluid loss.

Beta Blockers

Some drugs have similar shapes to neurotransmitters, enabling them to bind to receptors and block their activation.

Ion channel receptors

Ion channel receptors act as gates in the membrane; shape changes trigger opening.
Specific ions pass through the channel.
Examples: muscle contraction, nerve cell communication.
- The Na+/K+ ATPase is crucial for maintaining the membrane potential.

Summary

Cell signaling mechanisms (endocrine, paracrine, synaptic, and cell-cell contact).
Signal transduction pathways, receptor proteins
Example events: ligand-gated ion channels (e.g., Na+ influx), 7-transmembrane receptors (e.g., G protein activation), and receptor tyrosine kinases.
Second messengers (cAMP, DAG, IP3, Ca2+), and their roles in activating various enzymes and signal cascades.
Amplification of signaling events.
Inactivation mechanisms (i.e., removal of ligand, hydrolysis of GTP, activity of phosphatases and pumps).

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Description

This quiz explores key concepts related to cellular signaling pathways, focusing on the role of cAMP and protein phosphorylation cascades. Test your understanding of the second messengers involved and the targets of Protein Kinase A. Perfect for students studying cell biology or biochemistry.