20 Questions
What is the primary mechanism by which signal amplification is achieved in trkA receptor signal cascades?
Increasing the number of active signaling molecules at each stage in a cascade
Which of the following protein kinases is NOT involved in the trkA receptor signal cascade?
Src
What is the primary effect of CREB phosphorylation on memory formation?
Transcriptional regulation of gene expression
What is the role of cAMP in the context of trkA receptor signal cascades?
Activating PKA and phosphorylating CREB
What is the consequence of CREB knockout in mice?
Impaired memory formation and memory deficits
Which type of receptor is involved in the D1 receptor pathway?
G-protein coupled receptor
What is the effect of protein kinase cascades on pain pathways?
Amplification of pain transmission
What is the role of NGF in adults?
Released during tissue damage and inflammation, increasing excitability of sensory nerves
Which type of receptors does NGF bind to on peripheral neurons?
TrkA receptors
What is the result of activation of one receptor by a single extracellular transmitter molecule?
Synthesis of multiple second messengers and altered activity of multiple targets
What is the primary advantage of rapid on-off signals in cellular signaling?
Greater temporal resolution
Which of the following receptor classes is NOT associated with second messenger function?
Ligand-gated Ion Channels
What is the role of A-kinase anchoring proteins in cellular signaling?
To localize second messengers in specific microdomains
Which type of protein kinase is involved in the phosphorylation of effector enzymes downstream of G-protein Coupled Receptors?
Serine/Threonine Kinases
What is the primary consequence of convergent signaling pathways on a common target?
Integration of multiple signals to produce a coordinated response
Which of the following adenylate cyclase isoforms are activated by calcium/calmodulin?
Isoforms I, III, and VIII
What is the primary effect of cAMP binding to PKA?
PKA dissociates into a catalytic subunit and a regulatory subunit
What type of receptors are associated with adenylate cyclase activation?
G-protein Coupled Receptors
Which of the following is a target of PKA phosphorylation?
All of the above
Which subunit of PKA is responsible for cAMP binding?
Regulatory subunit
Study Notes
TrkA Receptor Signal Cascades
- TrkA receptor signal cascades amplify signals through multiple kinases, including Ras, Raf-1, PI-3-K, and PKC.
- Activation of trkA receptors leads to the activation of multiple downstream targets, including ERK1/2, Cytosolic targets, and Gene Expression.
Signal Amplification
- Signal amplification occurs by increasing the number of active signaling molecules at each stage in a cascade and using multiple pathways.
- Few primary messenger molecules can produce very diverse cellular responses.
- Signal amplification allows for sensitive and efficient signaling.
Spatio-Temporal Localisation
- cAMP influences memory formation through activation of PKA and CREB phosphorylation.
- Local [cAMP] levels influence memory formation, with short-term effects on phosphorylation and trafficking of glutamate receptors, Kv channels, and GABA receptors.
- Long-term effects occur through transcriptional regulation via CREB.
- CREB knockout mice have memory deficits and impaired patterns of neuronal hippocampal LTP firing.
Dopamine and cAMP Signaling
- Dopamine binds to D1 receptors, activating Adenylate Cyclase (AC) to produce cAMP.
- cAMP activates Protein Kinase A (PKA), which phosphorylates targets, including ion channels, enzymes, and transcription factors.
Nerve Growth Factor (NGF) and Pain
- NGF is synthesized by many different cell types and stimulates organ innervation.
- NGF drives neuronal proliferation and survival during nervous system development.
- In adults, NGF is released during tissue damage and inflammation, increasing the excitability of sensory nerves.
- NGF binds to trkA receptors on peripheral neurons, altering pain processing through altered gene expression.
Importance of Spatial and Temporal Localisation
- The rate of second messenger breakdown/removal is important for preventing unwanted signaling effects.
- Rapid on-off signals are more energetically efficient and provide greater temporal resolution.
- Spatial and temporal localisation of second messengers is important for signal specificity.
This quiz covers the trkA receptor signal cascades in neurons, including amplification mechanisms and protein interactions. It also explores the activation of various kinases and their effects on gene expression and cytosolic targets.
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