Lecture 5: Cellular Endocrine 2 Flashcards
(33 cards)
What is signal amplification?
- 1 hormone molecule binding to its cell receptor
- Triggers a cascade of second messengers
- Each second messenger may cause the activation or production of many other second messenger molecules
1 hormone molecule binding can end up producing 1 million molecules of the final product
What is signal transduction?
The process of converting a signal into a cellular response
What are the 4 mechanisms of signal transduction for peptide and catecholamine hormones?
- Change in the membrane potential e.g. neurons, skeletal muscle cells, cardiac muscle cells
Second messenger pathways:
- Increase in calcium concentration
- Phosphorylation of proteins
- Increase in gene transcription
Describe the mechanism for the increase in Ca2+ concentration:
- Activation and opening of membrane and/or ER calcium channels
- Calcium binds to proteins and changes their conformation and function: calmodulin (troponin)
- Activates kinases - kinases phosphorylate other molecules
Describe the mechanism of phosphorylating proteins:
Kinases phosphorylate other molecules:
* Phosphorylation can increase or decrease activity
Kinase + ATP -> Protein-P + ADP
What can be phosphorylated?
- Transcription factors
- Channels and transporters
- Enzymes
Describe the mechanism of increasing gene transcription:
- Hormone binds to metabotropic receptor
- Activation of proteins that function as transcription factors via phosphorylation or other means
- Primary gene responses in the nucleus -> mRNA -> synthesis of different transcription factors outside nucleus
- Responses of other genes in the nucleus -> mRNA -> synthesis of proteins that mediate the cell’s response to the 1st messenger e.g. proliferation and differentiation
How can gene transcription be regulated?
- Metabotropic receptors for peptide and catecholamine hormones (cell membrane)
- Steroid receptors (cytoplasmic/nuclear)
- Thyroid hormone receptors (nuclear)
What are ionotropic receptors?
An ion channel in the cell membrane that opens in response to a neurotransmitter or hormone binding
What are metabotropic receptors?
A receptor on the cell membrane that initiates a number of metabolic steps to regulate cell function
What are the 4 types of receptors for peptide and catecholamine hormones?
Ionotropic receptors (open ion channels):
- Ligand-gated ion channels
Metabotropic receptors (change cellular metabolism):
- Receptor tyrosine kinases
- Tyrosine kinase associated receptors
- G-coupled protein receptors (GPCRs)
What are the 3 steps in the signal transduction pathway for ionotropic receptors?
- When the hormone isn’t bound, the channel in the receptor is closed
- When the hormone (first messenger) binds the ion channel opens
- Causes a response in the cell via:
- Change in membrane potential
- Ca2+ influx
Give 2 examples of ionotropic receptors:
- Neuromuscular junction: nicotinic acetylcholine receptors
- Chemical synapses between neurons
What are the 4 steps in the signal transduction pathway for receptor tyrosine kinase?
- The hormone binds to metabotropic receptor
- Induces a conformational change so that the tyrosine kinase portion of the receptor is activated, causing it to phosphorylate its OWN tyrosine residues (autophosphorylation)
- The phosphorylated tyrosine’s act as docking sites for other proteins
- Proteins can dock and be phosphorylated or docking may bring them into proximity with other membrane bound proteins which they can interact with
Give an example of a receptor tyrosine kinase:
Insulin receptor
What are the 3 steps in the signal transduction pathway for tyrosine kinase associated receptor?
- The hormone binds to the receptor and induces a conformational change
- This leads to activation of the JAK kinase
- Janus Kinase
- Just Another Kinase - The activated kinase then phosphorylates tyrosine residues on other proteins, changing their cellular function.
Give 2 examples of a tyrosine kinase associated receptor:
- Prolactin
- GH receptors
What is a G-protein coupled receptor and what are it’s subunits?
- The receptor is a transmembrane protein
- It is associated with a G-protein, which has 3 subunits - alpha, beta & gamma
- Alpha subunit can bind GTP, GDP and can act as a GTPase; hydrolysing GTP to GDP + Pi
- Beta & gamma help to anchor the G-protein to the receptor
What are the 6 steps in the signal transduction pathway for G-protein coupled receptors?
- Receptor is activated, causing conformational change which changes the affinity of the alpha subunit so that it’s more likely to bind GTP
- Once bound to GTP, the alpha subunit dissociates from beta/gamma and can interact with effector proteins in the membrane:
* ion channels
* enzymes - After the alpha subunit has interacted with its effector proteins the alpha subunit acts as a GTPase; GTP → GDP + Pi
- This inactivates the alpha subunit
- It leaves the effector proteins and recombines with the other two subunits
- Ready to receive another signal
What are the 3 types of G-protein coupled receptors?
- Gs-protein
- Gi-protein
- Gq-protein
What are the 6 steps in the signal transduction pathway for Gs-protein coupled receptors?
- A hormone binds to the receptor, activating it
- GTP binds to alpha subunit of the Gs-protein, causing it to unbind from the rest of the Gs-protein
- GTP and aplha interacts with adenylyl cyclase and ACTIVATES IT
- Activated adenylate cyclase; ATP -> cAMP
- cAMP activates cAMP-dependent protein kinases e.g. Protein kinase A (PKA)
- Phosphorylation of proteins causes a cellular response; activate or inhibit
Give 2 examples of Gs-protein coupled receptors:
- Beta adrenergic receptors in the heart
- ADH (vasopressin) receptors in the kidney
What are the 4 steps in the signal transduction pathway for Gi-protein coupled receptors?
- A hormone binds to the receptor, activating it
- GTP binds to alpha subunit of the Gi-protein, causing it to unbind from the rest of the G-protein
- GTP and alpha interacts with adenylyl cyclase and INHIBITS IT
- Inhibition of adenylate cyclase causes:
↓ cAMP
↓ activation of PKA
↓ protein phosphorylation
Give 2 examples of Gi-protein coupled receptors:
- Muscarinic acetylcholine receptors in the heart
- Alpha-2 adrenergic receptors
