Signaaltransductie 1 Flashcards
Define signal transduction and its significance in cell regulation
Signal transduction is the process by which cells convert extracellular signals into a cellular response. It is crucial for cell communication and regulation, allowing cells to respond to changes in their environment and maintain homeostasis.
Explain how cells respond to extracellular signals through receptors
Cells respond to extracellular signals by binding these signals to specific cell surface receptors. Receptors can be membrane-bound or intracellular. Binding induces conformational changes in the receptor, leading to the activation of intracellular signaling pathways.
What is homeostasis, and how is it regulated by signal transduction? Provide examples.
Homeostasis is the maintenance of stable internal conditions in an organism. Signal transduction helps regulate homeostasis by allowing cells to respond to changes. For example, insulin signaling regulates blood glucose levels to maintain homeostasis.
Describe the role of feedback mechanisms in signal transduction. Give examples from cellular processes.
Feedback mechanisms in signal transduction regulate the intensity and duration of cellular responses. Negative feedback, like the inhibition of an enzyme in a pathway, helps maintain balance. Positive feedback, like the activation of blood clotting factors, amplifies responses.
Explain the concept of setpoints in homeostasis and how signal transduction can modify these setpoints.
Setpoints are ideal values for physiological parameters. Signal transduction can modify setpoints by adjusting the sensitivity or responsiveness of receptors. For instance, thermoregulation can be influenced by adjusting the setpoint for body temperature.
Define and describe the role of scaffold proteins in signal transduction. Provide an example of a scaffold protein.
Scaffold proteins assist in organizing and facilitating signal transduction by bringing together key signaling components. An example is KSR1 in the MAP kinase pathway, facilitating the activation of ERK.
Discuss the importance of post-translational modifications (PTMs) in regulating protein function. Give examples of PTMs.
PTMs, such as phosphorylation and ubiquitination, regulate protein function. Phosphorylation activates or deactivates proteins (e.g., activation of kinases). Ubiquitination marks proteins for degradation (e.g., proteasomal degradation).
Compare and contrast SH2 and SH3 domains in proteins. How do they contribute to signal transduction?
SH2 domains bind to phosphorylated tyrosine residues, mediating protein-protein interactions. SH3 domains bind to proline-rich motifs, facilitating the assembly of signaling complexes. Both domains contribute to signal transduction by promoting specific protein interactions.
Explain the significance of proximity-induced activation in signal transduction.
Proximity-induced activation occurs when signaling components are brought into close proximity, enhancing their interaction and promoting signal transduction. This can lead to efficient and specific activation of downstream components.
Describe the structural features of kinases and their role as molecular switches.
Kinases have conserved domains, such as the catalytic kinase domain, involved in transferring phosphate groups. They act as molecular switches by phosphorylating target proteins, thereby regulating their activity and cellular responses.
Discuss the insulin signaling pathway, focusing on the activation of mTOR through PKB/AKT.
Insulin activates PKB/AKT, which phosphorylates and inhibits TSC2. This leads to the activation of mTOR, promoting protein synthesis and cell growth.
Explain the concept of double inhibition in signal transduction pathways. Provide an example.
Double inhibition involves inhibiting an inhibitor. In the MAP kinase pathway, ERK phosphorylates and inhibits Raf kinase, creating a double-negative feedback loop.
Describe the role of second messengers in amplifying signals in signal transduction pathways.
Second messengers, like cAMP or Ca++, amplify signals by transmitting the original signal from the receptor to downstream effectors, leading to a robust cellular response.
Choose one of the five specified signal transduction pathways and outline its key components and functions.
Example: GPCR > AC > (PKA>CREB)/(EPAC/Rap1)
- GPCR activation leads to adenylyl cyclase (AC) activation.
- AC converts ATP to cAMP.
- cAMP activates protein kinase A (PKA) or EPAC/Rap1 pathways.
- PKA can phosphorylate CREB, affecting gene expression.
- EPAC/Rap1 regulates cellular processes like adhesion and migration.
Compare and contrast the activation mechanisms of protein kinases and monomeric GTPases.
Both kinases and monomeric GTPases act as molecular switches. Kinases switch between active (phosphorylated) and inactive states, while GTPases switch between GTP-bound (active) and GDP-bound (inactive) states.
Discuss the PIP3-mediated activation of PKB (AKT) in the insulin signaling pathway.
Insulin activates PI3K, leading to the production of PIP3. PIP3 recruits PKB/AKT to the membrane, where it is phosphorylated and activated by PDK1. Activated PKB/AKT promotes various cellular responses.
Explain how GTPases, such as Ras, are regulated by GEFs and GAPs.
Guanine nucleotide exchange factors (GEFs) activate GTPases like Ras by promoting the exchange of GDP for GTP. GTPase-activating proteins (GAPs) deactivate GTPases by enhancing GTP hydrolysis, converting GTP to GDP.
Describe the structural features of heterotrimeric G proteins and their role in signal transduction.
Heterotrimeric G proteins consist of α, β, and γ subunits. Upon GPCR activation, the α subunit dissociates and modulates downstream effectors, transmitting the signal.
Discuss the activation and function of GPCRs in signal transduction pathways.
GPCRs are activated by ligand binding, leading to conformational changes that enable interaction with G proteins. Activated GPCRs modulate intracellular signaling cascades, influencing various cellular processes.
Explain the role of GAPs in turning off GTPase-mediated signaling.
GAPs enhance GTP hydrolysis in GTPases, turning off signaling by promoting the inactive GDP-bound state.
Discuss the mechanisms involved in terminating GPCR-mediated signaling.
GPCR signaling is terminated by receptor desensitization, internalization, and degradation. Arrestins play a role in receptor desensitization and internalization.
How do cells ensure the termination of kinase-mediated signaling?
Cells terminate kinase-mediated signaling through various mechanisms. One common mechanism is through the action of phosphatases, enzymes that remove phosphate groups from proteins. For example, protein phosphatases can dephosphorylate kinases, reversing their activation and returning them to an inactive state.
Explain the role of ubiquitin-proteasome system in terminating signaling pathways.
The ubiquitin-proteasome system plays a crucial role in terminating signaling pathways by marking specific proteins for degradation. Ubiquitin, a small protein, is attached to target proteins, marking them for recognition and degradation by the proteasome. This process is essential for removing activated signaling components and ensuring the timely termination of cellular responses.
Discuss the concept of receptor downregulation in the context of signaling pathways.
Receptor downregulation involves a decrease in the number of cell surface receptors, reducing the cell’s responsiveness to a particular signal. This can occur through internalization and degradation of receptors, which is a mechanism to prevent excessive or prolonged signaling.
How does negative feedback contribute to the termination of signaling pathways?
Negative feedback mechanisms contribute to the termination of signaling pathways by inhibiting components of the pathway. For instance, activated downstream effectors can inhibit upstream components, creating a feedback loop that dampens the overall signal. This helps prevent prolonged activation and maintains cellular homeostasis.
Explain how dysregulation of signal transduction pathways can contribute to diseases.
Dysregulation of signal transduction pathways can contribute to diseases by causing abnormal cell behavior. For example, mutations leading to constitutive activation of growth factor receptors can result in uncontrolled cell proliferation, contributing to cancer.
Discuss the therapeutic implications of targeting specific components in signal transduction pathways.
Targeting specific components in signal transduction pathways has therapeutic implications, especially in diseases where these pathways are dysregulated. For instance, kinase inhibitors are used in cancer treatment to block aberrantly activated kinases, limiting tumor growth.
Which enzyme is responsible for adding phosphate groups to proteins in kinase-mediated signaling?
A) Protease
B) Ligase
C) Phosphatase
D) Kinase
D
