Intracellular Signaling and Cellular Responses

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Questions and Answers

What happens to the G-protein after GTP binds to its alpha subunit?

The G-protein becomes inactive and reassociates.

The G-protein directly activates the receptor.

The G-protein dissociates into alpha and beta-gamma subunits. (correct)

The G-protein remains unchanged.

Which of the following describes the role of cAMP in the activation of Protein Kinase A (PKA)?

cAMP inhibits the activity of PKA.

cAMP binds to the regulatory subunits leading to dissociation. (correct)

cAMP acts as a substrate for PKA.

cAMP directly phosphorylates target proteins.

What is the ultimate result of PKA activation in glycogen metabolism?

Activation and breakdown of glycogen. (correct)

Increased glycogen synthesis.

Inhibition of glucose production.

Direct inhibition of phospholipase C.

What is the role of phospholipase C in the signal transduction pathway involving Gαq?

It cleaves inositol phospholipids to form DAG and IP3. Signup and view all the answers

How does IP3 affect intracellular calcium levels?

It activates calcium channels in endoplasmic reticulum, increasing calcium concentration. Signup and view all the answers

What is the effect of protein kinase C (PKC) in the signaling pathway initiated by Gαq?

PKC is activated by DAG and calcium. Signup and view all the answers

What role does CREB play in response to cAMP signaling?

CREB promotes transcription of specific genes. Signup and view all the answers

Which enzyme is responsible for the degradation of cAMP?

Phosphodiesterase. Signup and view all the answers

What type of enzyme is adenylyl cyclase?

A cyclase that converts ATP to cAMP. Signup and view all the answers

What is a role of glucagon in cellular responses?

Switches liver metabolism from synthesising glycogen to breaking it down Signup and view all the answers

Which of the following substances is NOT considered an extracellular signal?

ATP Signup and view all the answers

What defines a second messenger in signal transduction?

Small molecules that relay signals received at cell surface receptors Signup and view all the answers

Which of the following is a role of G proteins in signal transduction pathways?

Facilitate cellular response to extracellular signals by transmitting signals from receptors Signup and view all the answers

What is the significance of transmembrane receptors in cellular signaling?

They control gene activity through associated signaling pathways Signup and view all the answers

What triggers the autophosphorylation of tyrosine residues in the receptor tyrosine kinase (RTK)?

Binding of EGF Signup and view all the answers

What is the role of GTP-Ras in cellular signaling?

It triggers a kinase cascade Signup and view all the answers

Which of the following is NOT a function of G-protein coupled receptors (GPCR)?

Directly activate kinase cascades Signup and view all the answers

What is the characteristic feature of the Ras-MAP kinase pathway?

Triggers activation of transcription factors Signup and view all the answers

What is meant by 'cross talk' in cellular signaling?

Different signals trigger pathways that block each other Signup and view all the answers

Which of the following processes is characteristic of receptor tyrosine kinases (RTK)?

Direct activation of a kinase cascade Signup and view all the answers

How do different hormones with different receptors lead to similar cellular effects?

By converging on similar pathways Signup and view all the answers

Which protein facilitates the exchange of GDP for GTP in the Ras-MAP kinase pathway?

Sos Signup and view all the answers

What is the role of acetylcholine in relation to nicotinic receptors?

It activates the receptor leading to ion exchange. Signup and view all the answers

What feature is common to steroid hormones?

They contain hormone and DNA binding domains. Signup and view all the answers

Which molecule acts as a second messenger in response to signals?

cAMP Signup and view all the answers

What initiates the generation of second messengers in GPCR signaling?

Conformational change in the receptor upon ligand binding. Signup and view all the answers

What is the state of G-proteins when they are inactivated?

They are part of a heterotrimeric complex bound to GDP. Signup and view all the answers

What happens to G-proteins when GTP binds to them?

They dissociate and become active. Signup and view all the answers

What is the function of inositol 1,4,5-trisphosphate (IP3) in cellular signaling?

It releases Ca2+ from the endoplasmic reticulum. Signup and view all the answers

Which domains are involved when steroid hormones activate transcription factors?

Hormone binding, DNA binding, and transcription factor interaction. Signup and view all the answers

What type of signaling involves a signal acting on the same cell that produces it?

Autocrine Signup and view all the answers

Which type of receptor is activated by hydrophilic hormones such as adrenaline?

Cell surface receptor Signup and view all the answers

What occurs when a signal binds to its receptor?

Direct activation of transcription factor Signup and view all the answers

What type of signaling uses electrical signals transmitted down a cell?

Neuronal Signup and view all the answers

Which component is responsible for generating a secondary message inside the cell?

Binding of glucagon leading to cAMP production Signup and view all the answers

In paracrine signaling, how does the signal affect other cells?

It acts on neighboring cells very close to the producing cell. Signup and view all the answers

What must a cell express in order to respond to a signal?

The appropriate receptor Signup and view all the answers

How does a hormone that is hydrophobic interact with its receptor?

It crosses the plasma membrane and binds in the cytosol. Signup and view all the answers

Signup and view all the answers

Study Notes

Intracellular Signalling

Cells signal to each other in various ways
A "second messenger" is a molecule that relays a signal from a cell membrane receptor to the inside of a cell, initiating a response
Transmembrane receptors and their associated signaling pathways are crucial for controlling gene activity
G proteins, cAMP, phospholipase C, diacylglycerol (DAG), inositol triphosphate (IP3), and Receptor Tyrosine Kinase (RTK) play vital roles in signal transduction pathways
Metabolic processes can be regulated through intracellular signaling
Signal pathways can overlap, and intracellular signaling is vital for drug action

Cellular Responses

Cells change metabolic activities. For instance, glucagon can cause liver cells to switch from glycogen synthesis to glycogen breakdown
Binding of an antigen to a mast cell triggers histamine release
Changes in gene expression. Examples include epidermal growth factor (EGF) initiating cell growth and light activation of rhodopsin
Extracellular signals that drive these responses can include amino acids and their derivatives, steroids, prostaglandins, proteins and peptides, and gases

Different Ways for Cells to Signal

Endocrine: Signals produced in one part of the body travel through the bloodstream to target cells elsewhere
Autocrine: Signals act on the same cell that produces them
Paracrine: Signals act on neighboring cells
Contact dependent: Signals involve direct interaction between cells
Neuronal: Electrical signals transmitted along neurons, with messages passed to other cells via synapses

Receptor/Signal

Cells must have specific receptors to respond to signals
Receptors are highly selective and have high affinity for their target signals
Signals can bind to various receptor types
Signals are eventually deactivated

Location of Receptor

Cell surface receptor: Hydrophilic signals (such as adrenaline) bind to receptors on the cell surface, triggering intracellular responses
Intracellular receptor: Hydrophobic signals (like steroid hormones) cross the cell membrane and bind to intracellular receptors, initiating responses within the cell

Types of Signaling

Signals can bind to receptors, causing membrane depolarization (e.g., acetylcholine) or direct activation of transcription factors (e.g., steroids)
Signals can trigger the generation of secondary messengers like cAMP (e.g., glucagon) to activate kinase cascades (e.g., EGF)

Ion-Channel Coupled Receptors

Ion channel-coupled receptors respond to signals through ion flow (e.g., acetylcholine binding to nicotinic acetylcholine receptors) causing membrane depolarization

Direct Activation of Transcription Factors

Steroid hormones have hormone binding domains, DNA binding domains, and domains for interaction with other transcription factors
Binding induces conformational changes allowing DNA binding and activation of transcription
These are ligand-dependent transcription factors

Secondary Messengers

Signal molecules are first messengers. Secondary messengers can include cyclic AMP (cAMP), cyclic GMP, IP3/DAG, and Calcium
Second messengers are triggered by enzymes and generate intracellular responses

G-protein-Coupled Receptor (GPCR)

GPCRs are integral membrane proteins linked to G proteins.
Adrenaline is an example, activating adenylyl cyclase (adenylate cyclase) which creates cAMP.
The activation of phospholipase C leads to the formation of IP3 and DAG

Guanine Nucleotide Binding Proteins (G-proteins)

G-proteins are heterotrimeric complexes with alpha, beta, and gamma subunits
They exist in an inactive state bound to GDP and an active state bound to GTP.
G-protein activation involves dissociation of the alpha subunit, which then activates effector enzymes

GPCR Signaling to Effector Enzymes

A signal molecule binds to the receptor triggering a response in the target cell
The G protein dissociates and activates an effector enzyme
The effector enzyme produces a second messenger
The G protein complex re-associates and the signaling ends

cAMP Dependent Protein Kinase A (PKA)

PKA is a tetrameric enzyme with regulatory and catalytic subunits
cAMP binding to regulatory subunits causes dissociation and activation of catalytic subunits. This is important for metabolic regulation.
A kinase cascade is typical, amplifying the signal

cAMP Mediated Effects on Glycogen Breakdown

Hormones like glucagon activate a cascade, causing glycogen breakdown, while glycogen synthesis is inhibited

Signal Amplification

Kinase cascades amplify hormonal signaling by increasing at each step in the cascade

cAMP

cAMP is formed via adenylyl cyclase, and deactivated by phosphodiesterase

cAMP and Gene Transcription

PKA phosphorylates the CREB (cAMP response element binding protein), activating the transcription of specific genes, important for long-term responses

GPCR and IP3/DAG

Some GPCR activate phospholipase C and generate IP3 and DAG, raising intracellular Ca2+ and activating protein kinase C

Receptor Activation of Phospholipase C

Signal molecules activate GPCR’s triggering a signaling cascade culminating in activation of protein kinase C. IP3 and DAG are involved.

Direct Activation of Enzymatic Kinase Cascade

Ligands like EGF cause autophosphorylation of receptor tyrosine kinase (RTK) domains.
Adaptor proteins like Grb2 bind to receptor, leading to GDP/GTP exchange on Ras, which drives kinase cascades that activate transcription factors

Ras as a G-protein

Ras is a monomeric G-protein
GTP-Ras triggers a kinase cascade, including MAPK, in response to growth signals

Overlap

Hormones can trigger different receptors or different pathways, leading to common effects
Different signals can converge on the same intracellular pathway
"Cross-talk" occurs when pathways block or influence one another

Summary

Extracellular signals activate receptors, which then trigger responses within the target cell, including via cAMP pathways, IP3/DAG pathways, or direct kinase cascade activation. Ligand-receptor activation can also influence gene transcription.

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Description

This quiz explores the intricate mechanisms of intracellular signaling and how cells respond to various external stimuli. Topics include second messengers, transmembrane receptors, and the roles of G proteins and related molecules in signal transduction. Understanding these processes is crucial for grasping metabolic regulation and drug action.