Cell Cycle and Signaling Pathways Quiz

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Questions and Answers

What characterizes the cell cycles during early embryonic development?

Presence of a restrictive checkpoint in G1.

Extended S phases without mitosis.

Rapid division without growth. (correct)

Long G1 and G2 phases for growth.

Which phase of the cell cycle is most affected by nutrient availability in Saccharomyces cerevisiae?

G1 phase at START. (correct)

G0 phase.

S phase.

M phase.

What occurs if growth factors are absent during the G1 phase of an animal cell?

Cells enter a quiescent stage (G0). (correct)

Cells immediately enter S phase.

Cells undergo apoptosis.

Cells replicate their DNA and continue to divide.

What is the role of cell cycle checkpoints?

To monitor and halt the cycle if DNA is damaged. Signup and view all the answers

Which fluorescence intensity peaks indicate cellular DNA content in the cell cycle analysis?

Two peaks corresponding to 2n for G1 and 4n for G2/M phases. Signup and view all the answers

What role does phosphorylation play in the function of Elk-1 as a transcriptional activator?

It stimulates the activity of Elk-1. Signup and view all the answers

Which of the following accurately describes the function of scaffold proteins in MAP kinase cascades?

They organize signaling cascades for effective signal propagation. Signup and view all the answers

What is the immediate effect of growth factor stimulation on the FOXO transcription factor?

It phosphorylates FOXO and retains it in the cytoplasm. Signup and view all the answers

In the PI 3-kinase/Akt signaling pathway, what is the primary substrate for the conversion to PIP3?

PIP2 Signup and view all the answers

What happens to FOXO in the presence of growth factors according to the signaling pathway described?

FOXO remains inactive in the cytoplasm due to sequestering. Signup and view all the answers

What is the role of GTP-binding proteins in signaling pathways?

They are involved in the transduction of extracellular signals. Signup and view all the answers

How does the binding of integrins to the extracellular matrix affect cell behavior?

It induces integrin clustering and activation of signaling pathways. Signup and view all the answers

What is the primary difference between receptor protein-tyrosine kinases and non-receptor tyrosine kinases?

Non-receptor tyrosine kinases have intrinsic kinase activity unlike receptor tyrosine kinases. Signup and view all the answers

In the context of G-protein coupled receptors (GPCRs), what effect would inhibiting cAMP phosphodiesterase (PDE) have on thyroid cell proliferation?

It would enhance thyroid cell proliferation by increasing cAMP levels. Signup and view all the answers

What is the role of phosphorylation by IκB kinase in the NF-κB signaling pathway?

It marks IκB for degradation by ubiquitylation. Signup and view all the answers

What types of receptors are specifically mentioned for binding to signal molecules in cell signaling?

Both A and B. Signup and view all the answers

How does NF-κB participate in feedback regulation?

By activating the transcription of IκB to inhibit its own activity. Signup and view all the answers

What distinguishes the cell cycle behavior of nerve cells and muscle cells compared to other somatic cells?

They become specialized and lose the ability to divide. Signup and view all the answers

What is the primary function of the PI 3-kinase pathway in relation to other signaling cascades?

It facilitates positive and negative crosstalk with the ERK pathway. Signup and view all the answers

What characterizes cells that do not typically divide but can be induced to do so?

They require external stimuli to initiate DNA synthesis. Signup and view all the answers

Study Notes

Cell Structure Overview

Cell signaling is a chapter in the broader field of cell biology, covering how cells communicate and respond to signals.

Extracellular Signal Molecules and Receptors

Extracellular signal molecules bind to specific receptors on the cell surface or within the cell.
Cell-surface receptors bind hydrophilic signal molecules.
Intracellular receptors bind small, hydrophobic signal molecules, often carried by carrier proteins.

Intracellular Signaling Pathways

Extracellular signals initiate intracellular signaling pathways.
These pathways involve intracellular signaling proteins that relay and amplify the signal.
They often involve phosphorylation cascades or GTP-binding proteins.
Effector proteins ultimately carry out the cellular response, altering metabolism, gene expression, or cytoskeletal movement.

Types of Receptors

Receptor types include steroid hormone receptors, G-protein-coupled receptors (GPCRs), receptor protein-tyrosine kinases (RTKs), non-receptor protein-tyrosine kinases, and ligand-gated channels.
Specific receptors exist for B and T cells, showcasing the body’s immune response.

Signaling by Phosphorylation

Kinases and phosphatases are frequent components of intracellular signaling pathways, where phosphorylation/dephosphorylation are key mechanisms.
Phosphorylation often activates proteins, while dephosphorylation inactivates them.
GTP-binding proteins are essential parts of signaling pathways, switching between active (GTP-bound) and inactive (GDP-bound) states.

cAMP Phosphodiesterase (PDE)

PDE enzymes break down the cyclic AMP (cAMP) second messenger molecule, which can affect thyroid cell proliferation.
Inhibiting PDE would increase cAMP levels.

Receptor Tyrosine Kinases (RTKs)

These receptors, activated by growth factors, initiate downstream signaling cascades that can lead to cell proliferation.
The activated receptor tyrosine kinase can phosphorylate other proteins (downstream signaling molecules).
SH2 domains bind to specific phosphotyrosine-containing peptide sequences on the activated receptors.

Non-receptor Tyrosine Kinases

These are not intrinsic to the receptor itself but are associated proteins involved in signaling.
Ligand binding triggers the dimerization of the receptor, enabling cross-phosphorylation and thus activation of associated nonreceptor tyrosine kinases.
Kinases phosphorylate tyrosine residues on the receptor, creating sites for downstream signaling molecules.

Integrin Signaling via FAK

Integrins are receptors that connect cells to the extracellular matrix (ECM), influencing cell behavior.
The non-receptor tyrosine kinase FAK is crucial in integrin signaling.
Integrin binding leads to FAK activation by autophosphorylation.
Src then phosphorylates FAK, creating more downstream signaling sites.

Ras Proteins and Ras-MAP Kinase Cascades

Ras is an important G protein, crucial for multiple signaling pathways, embedded in cell membranes via a lipid anchor.
Ras proteins are activated by GTP/GDP binding and play a significant role in cell signaling.
Oncogenic Ras versions cause unregulated cell proliferation, commonly implicated in cancer growth.

Generalized Ras-MAP Kinase Cascade

Growth factor binding triggers receptor activation, initiating a complex series of protein phosphorylations.
This results in the activation of transcription factors, ultimately regulating cell proliferation via downstream signaling pathways.
The cascade typically includes three kinase levels (MAPKKK, MAPKK, MAPK).

ERK Downstream Signaling

Activated ERK (extracellular signal-regulated kinase) translocates to the nucleus.
ERK then phosphorylates transcription factors such as Elk-1. These complexes (with SRF) bind to the serum response element (SRE) in the DNA.
Consequently, genes related to cell proliferation are upregulated, leading to more cell growth.

MAP Kinase Activation

Mammalian cells have multiple interconnected MAP kinase cascades to control diverse cellular functions, such as proliferation, differentiation, survival, inflammation, and cell death responses.
Different cascades respond to distinct stimuli (such as growth factors versus inflammatory cytokines), with shared components and crosstalk between them.
Several key kinases are important to consider (e.g. ERK, JNK, p38).

Scaffold Proteins

Scaffold proteins organize signaling cascades to bring components into close proximity, increasing the efficiency of signal transduction.
Through proximity, signaling cascades can be regulated and occur faster, increasing the efficacy and precision of the proteins involved in the pathways.

Second Messengers

Second messengers are intracellular substances, triggered by a first messenger (ligand), released into the cell interior after receptor binding on the cell surface.
They amplify signals and may affect various cellular processes; include phospholipid-derived molecules (such as inositol triphosphate) as well as cyclic AMP (cAMP) and nitric oxide.

Phosphatidylinositol-Derived Second Messengers

Phosphatidylinositols, PI(4,5)P2 and PI(3,4,5)P3, are critical to cellular messaging.
Specific enzymes act on these key molecules in cell membranes, and the resultant molecules relay signals or induce cellular pathways.

PI 3-Kinase/Akt Pathway

The PI3-kinase/Akt pathway is crucial for regulating cell growth, survival, and metabolism.
PI-3-kinase phosphorylates PIP2, forming PIP3, which recruits other proteins, including Akt, to the cell membrane.
Akt activates diverse downstream targets by phosphorylation.

FOXO Regulation

FOXO is a transcription factor affecting gene expression and is regulated by Akt/PI3K pathways.
Growth factor signaling inhibits FOXO nuclear activity, which plays a key role in cell growth/survival.
In the absence of growth factors, FOXO is de-phosphorylated and translocates to the nucleus, turning on genes essential to survival.

NF-κB Signaling

NF-κB (a transcription factor) is part of a critical signaling pathway activated by tumor necrosis factor receptor (TNF) activation.
TNF receptor activation initially leads to the recruitment of adaptor proteins to initiate the IKB kinase pathway.
Phosphorylated IKB is targeted for ubiquitin and proteasome degradation, releasing NF-κB to enter the nucleus and promote target gene expression.

Feedback Loops and Signaling Dynamics

Feedback loops are key parts of signaling pathways, as they maintain a balance and allow for fine-tuning of cellular responses.
These critical loops, involving gene activation/regulation of IKB for NF-κB, affect signaling dynamics and cellular activity.

Crosstalk between Pathways

Signaling pathways frequently interact, influencing each other through positive or negative feedback loops.
The ERK and PI-3-kinase/Akt pathways exhibit significant crosstalk, showing how different signaling systems may influence each other.

The Eukaryotic Cell Cycle

Eukaryotic cells are governed by a conserved cell cycle with distinct phases regulated by multiple checkpoints controlling the cell cycle (G1, S, G2, M).
Cell cycles in different organisms have variations in the length of their phases.

Embryonic Cell Cycles

Embryonic cell cycles lack G1 and G2 phases during early divisions, focusing primarily on cell division (S and M phases).
Key cell cycle research is based on temperature-sensitive mutant yeast used to elucidate and test these mechanisms.

DNA Content Determination

Flow cytometry is a useful tool to evaluate the DNA content of cells during the cell cycle.
Distinctive DNA content peaks allow the identification of cells in particular phases (G1/G2/M/S).

Cell Cycle Regulation in Budding Yeast

Budding yeast (Saccharomyces cerevisiae) illustrates a key cell cycle regulation point in G1 called Start.
Regulation here depends on factors like nutrient availability and cell size.

Animal Cell Cycles and Growth Factors

Animal cell cycles have a restriction point in G1, analogous to Start in yeast.
Cell entry into quiescence in G0 occurs in the absence of growth factors.

Cell Cycle Checkpoints

Cell cycle checkpoints ensure accuracy and integrity. Damaged DNA is repaired or the cycle is halted to ensure accurate replication.
These include checkpoints in G1, G2, and mitosis to address any DNA damage. DNA replication problems can also trigger arrests at these checkpoints. The spindle assembly checkpoint is an example of a mitosis-specific checkpoint.

Eukaryotic Cell Cycle Regulators

Eukaryotic cell cycle progression is governed by a conserved set of protein kinases called Cyclin-dependent kinases (CDKs) and their regulatory subunits, called cyclins.
These kinases, and their cyclin partners, are fundamental to driving cell cycle progression.

Maturation Promoting Factor (MPF)

MPF is a protein kinase complex (cyclin-dependent kinase and cyclin) that triggers entry into M (mitosis) phase, based on levels of cyclin.
In frog oocytes, MPF activation is triggered by progesterone, initiating cell division.

Cyclin Regulation

Cyclins are key regulators, fluctuating throughout the cell cycle and in response to extracellular signals.
Specific cyclin pairs drive the cell through various phases (e.g., cyclin D and cyclin-dependent kinases Cdk4 and Cdk6).

Cdk Inhibitors

Cyclin-dependent kinases are also regulated by inhibitors, including those belonging to the Ink4 and Cip/Kip family.
These inhibitors are essential in monitoring the cycle progression and ensuring that there are no irregularities.

D-Type Cyclins

In animal cells, D-type cyclins are important for activating Cdk4/Cdk6, and they are a crucial link between the activity of growth factors and cell cycle progression.
These drive cell cycle progression through the restriction point.

Rb Protein Regulation

In its underphosphorylated form, Rb binds to the E2F transcription factor, preventing cell cycle progression.
Phosphorylation of Rb by cyclin-dependent kinases (CDK4/6) releases E2F and activates genes required for cell cycle progression.

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Description

Test your knowledge on the cell cycle dynamics during early embryonic development and the impact of nutrients on yeast. Explore the roles of growth factors, cell cycle checkpoints, and signaling pathways like PI 3-kinase/Akt in cell regulation.