Questions and Answers
What is the primary function of transmembrane receptors in cellular signalling?
Which of the following is NOT an example of a second messenger?
What is the primary function of G proteins in signal transduction pathways?
Which of the following is an example of a cellular response to extracellular signals?
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What is the role of phospholipase C in signal transduction pathways?
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Which of the following is an example of an extracellular signal that binds to a transmembrane receptor?
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What is the role of Receptor Tyrosine Kinase (RTK) in signal transduction pathways?
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Which of the following is an example of a cellular response to extracellular signals that involves changes in gene expression?
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What is the primary characteristic of a paracrine signal?
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Which type of receptor is typically associated with hydrophilic hormones such as adrenaline?
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What is the primary difference between autocrine and paracrine signaling?
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What is a characteristic of receptors in terms of their binding to signals?
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Which type of signaling involves the direct interaction between two cells?
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What is a characteristic of signals in terms of their binding to different receptors?
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What is the primary mechanism of action for steroid hormones?
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What is the effect of acetylcholine binding to its receptor?
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What is the function of the DNA binding domain in steroid hormones?
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What is the role of G-protein-coupled receptors in signaling pathways?
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What is the effect of glucagon binding to its receptor?
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What is the function of the hormone binding domain in steroid hormones?
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What is the effect of EGF binding to its receptor?
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What is the role of phospholipase C in signaling pathways?
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What is the main function of the G-protein α subunit when GTP is bound to it?
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What is the result of the GTPase activity on the G-protein α subunit?
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What is the function of the βγ subunit in the G-protein complex?
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What is the result of the signal binding to the receptor in GPCR signalling?
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What is the function of the effector enzyme in GPCR signalling?
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What is the purpose of the GTP/GDP exchange on the G-protein?
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What is the outcome of GTP hydrolysis in the G-protein complex?
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What is the role of cAMP in the activation of protein kinase A (PKA)?
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What is the effect of phosphorylase kinase a on glycogen?
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What is the role of phosphodiesterase in the regulation of cAMP levels?
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What is the outcome of CREB phosphorylation by PKA?
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What is the outcome of IP3 binding to the Ca2+ channel in the endoplasmic reticulum?
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What is the role of DAG in the activation of protein kinase C?
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What is the outcome of signal amplification via kinase cascade?
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What is the role of Gαq (Gq) subunit in the GPCR pathway?
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What is the outcome of the binding of cAMP to the regulatory subunit of PKA?
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Study Notes
Cell Biology and Signalling
- The course covers the foundations of medical science, specifically cell biology and signalling.
Cellular Responses
- Cellular responses to signals include:
- Change in metabolic activities (e.g. glucagon switches liver from synthesizing glycogen to breaking down glycogen)
- Secrete and release (e.g. binding of antigen to mast cell stimulates the secretion of histamine)
- Changes in gene expression (e.g. Epidermal Growth Factor (EGF) activating genes involved in cell growth)
- Sensory perception (e.g. light activation of rhodopsin)
Extracellular Signals
- Factors that act as extracellular signals include:
- Amino acids (and derivatives) (e.g. glutamate, adrenaline, dopamine)
- Steroids (e.g. oestradiol, testosterone, cortisol, aldosterone)
- Prostaglandins (eicosanoids) derived from arachidonic acid
- Proteins and Peptides (e.g. insulin, glucagon, growth factor, EGF)
- Gases (e.g. NO, CO)
Ways for Cells to Signal to Each Other
- Different ways for cells to signal to each other include:
- Endocrine (signal produced by cells in one part of the body and travels in blood to target cells somewhere else)
- Autocrine (signal acts on the same cell that produces it)
- Paracrine (signal produced by cell and acts on other cells that are very close)
- Contact dependent (signal is integral part of one cell and interacts directly with another cell)
- Neuronal (electrical signal transmitted down cell and message passed to another via synapse)
Receptor/Signal
- A cell must express a receptor in order to respond to a signal
- Receptors have high selectivity and high affinity
- Signals can bind to different types of receptors
- Signals are eventually turned off
Location of Receptors
- Cell surface receptors (e.g. hormone is hydrophilic, binding of hormone triggers response inside cell)
- Intracellular receptors (e.g. hormone is hydrophobic, hormone crosses the plasma membrane, hormone binds to receptor in the cytosol and triggers a response inside cell)
Types of Signalling
- Binding of signal to receptor:
- Depolarization of membrane due to flow of ions (e.g. acetylcholine)
- Direct activation of transcription factor (e.g. steroid)
- Generation of secondary message inside cell (e.g. glucagon – cAMP)
- Direct activation of enzymatic kinase cascade (e.g. EGF – MAP kinase pathway)
Second Messengers
- Cyclic AMP (cAMP)
- Cyclic GMP (cGMP)
- Inositol 1, 4, 5-trisphosphate (IP3)
- Diacylglycerol (DAG)
- Calcium ions (Ca2+)
G-Protein-Coupled Receptors
- G-protein-coupled receptors (GPCRs) have 7 transmembrane-spanning domains
- Activation of GPCRs leads to the activation of G-proteins
- G-proteins are guanine nucleotide binding proteins
G-Protein Signalling
- G-protein signalling involves:
- Signal binding to receptor
- G-protein (GDP bound) associates with receptor
- GTP/GDP exchange on G-protein (GTP bound)
- G-protein dissociates into α (GTP bound) and βγ subunits
- α subunit (with GTP bound) activates effector enzyme
- Effector enzyme produces 2nd messenger
- GTP hydrolysed to GDP, G-protein complex re-associates, signalling ends
cAMP Signalling
- cAMP is a second messenger produced by the activation of adenylyl cyclase
- cAMP activates protein kinase A (PKA)
- PKA phosphorylates and activates target proteins
cAMP Dependent Protein Kinase A (PKA)
- PKA is a tetrameric enzyme consisting of 2 regulatory (R) and 2 catalytic (C) subunits
- cAMP binds to the regulatory subunit and tetramer dissociates
- Catalytic monomers (C) are now active enzymes
cAMP Mediated Effects on Glycogen Breakdown
- cAMP dependent protein kinase (PKA) phosphorylates and activates phosphorylase kinase
- Phosphorylase kinase phosphorylates and activates phosphorylase
- Phosphorylase breaks down glycogen to glucose-1-phosphate
Signal Amplification via Kinase Cascade
- Signal amplification occurs through the activation of multiple enzymes in a kinase cascade
- The numbers of molecules involved in each step of the cascade increase, amplifying the signal
cAMP and Gene Transcription
- PKA phosphorylates CREB (cAMP response element binding protein)
- CREB binds to specific sequences in target genes and stimulates transcription
- Long-term adaptation to starvation involves changes in gene expression
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Description
Quiz on cell biology and signalling, covering cell-to-cell signalling, second messengers, and transmembrane receptors in biochemistry.