Signal Transduction and G Protein-Coupled Reactions Flashcards
How do hydrophobic hormones diffuse through the cell?
Through the cell membrane and activate cytosolic receptors.
How do hydrophobic hormones diffuse through the cell.
They bind to plasma membrane receptors and activate signal transduction pathways.
Some plasma membrane receptors activate G-protein switch proteins that trigger a variety of 1. __________ or induce the generation of 2. ______________.
- Downstream pathways
- Intracellular second messagers
What do Tyrosine Kinases do?
Trigger signal transduction pathways involving sequential activation of downstream kinases.
Give three examples of hydrophobic signals in the cell.
- Steroids
- Retinoids
- Thyroxine
Give three examples of hydrophilic signals in the cell.
- Small molecules
- Peptides
- Proteins
Cells respond to environment signals such as?
- Temperature
- Light
- Oxygen
- Sounds
- Odurs
Give examples of ways cells respond to signals from other cells.
- Hormones
- Growth factors
- Neurotransmitters
What is signal transduction?
The process of sensing external stimuli and conveying the information to intracellular targets.
Extracellular signal –> Intracellular space
Describe the process of hydrophobic signalling molecules.
- Hydrophobic hormones diffuses through the cell membrane into the cytoplasm.
- In the cytoplasm, the hormone binds to a receptor/activator. Very often the receptor is a transcriptional activator residing in the nucleus
- The receptor-hormone complex is recognized by a transporter molecule that takes it to the nucleus.
Some receptors are in the nucleus and are activated by the hormone.
What is ‘Dex’? What does it activate?
Dexamethasone activates the Glucocorticoid receptor.
In the absence of ‘Dex’, where is the Glucocorticoid receptor.
In the cytoplasm
In the presence of ‘Dex’, where is the receptor-hormone complex moved to?
Moved to the nucleus when the hormone activates the receptor site.
The control b-galactosidase is _________ regardless of the presence of ‘Dex”.
Cytoplasmic
Hydrophilic signalling molecules work differently than hydrophobic signalling molecules. Describe the reaction that takes place to enter the cell and the nucleus.
- The binding of the signal molecule to a specific cell surface receptor changes he conformation (shape) of the receptor and its activation.
- The activated receptor initiates downstream signal transduction proteins and/or second messengers.
- Signal transduction leads to the activation of effector protein(s) causing:
- Short term responses (Modification of cellular metabolism, function, movement)
- Long term responses in the nucleus (Modification of gene expression, development)
- Termination (or down-regulation) from negative feedback or removal of the extracellular signal from the receptor.
Membrane receptors bind only a single type of _________ signalling molecules.
Hydrophilic
All hormone receptors are highly _______ for their ligands.
Specific
Each receptor binds only a ______ type of hormone.
Single
When a hormone binds to its specific receptor, the hormone changes the _________ of the receptor sending a signal to the cascade.
Conformation
Give examples of small molecules, peptides, and proteins that are used for hydrophilic signalling molecules.
Small molecules: Adrenaline, acetylcholine
Peptides: Glucagon
Proteins: Insulin, growth hormones
List the four types of extracellular signalling.
- Endocrine signalling
- Paracrine signalling
- Autocrine signalling
- Signalling by plasma-membrane attached proteins
Describe endocrine signalling.
Affects target cells some distance from the site of synthesis.
- Far proximity
- Hormone gets secreted into the blood by the endocrine gland through the blood vessel and is secreted to the distant target cells
- Uses the blood and blood stream
Describe paracrine signalling.
Affects target cells in close proximity.
- Uses secretory cells to secrete hormones to the adjacent target cell.
Describe autocrine signalling.
Cells respond to the signals they produce. The target sites are ON the SAME cell.
- Hormone produced by the SAME cell targets the receptor sites on that cell.
Describe signalling by plasma-membrane-attached proteins.
The signalling cell it attached to the adjacent target cell and the hormones contact the specific receptor and they stay attached.
Proteins can be modified by multiple protein ________ or ___________.
Kinases or phosphatases
How can kinase/phosphatase activity be regulated?
- Phosphorylation
- Binding to other proteins
- Binding of second messenger small molecules
Phosphorylation can _______ or __________ protein function.
Activate or inhibit
Specific protein phosphatases oppose the effects of kinase by _____________ .
Removing the phosphate .
What are the two types of kinases in animal cells?
Tyrosine (Y) kinases and Serine (S)/Threonine (T) kinases
Describe G proteins: GTPase switch proteins
- Hydrophilic hormones bind to membrane receptors
- The G-protien coupled receptors (GPCR) activate G-protiens (GTPase switch proteins)
- G-protiens exchange GDP to GTP leading to a conformational change and activation
An active G-protein sends a ___________.
Signal
G-protein has intrinsic GTPase activity, which can be accelerated by _____________ (GAPs)
GTPase-accelerating proteins (GAPs)
Once the initial signal is sent, the G-protein inactivates itself. How does it do this?
It inactivates itself y hydrolyzing GTP to GDP
How is G-protein activity regulated?
It is regulated by the exchange of GDP to GTP.
Does association with the GTP switches the protein on or off?
On.
After sending the signal, GTP is ______ and the protein is switched “off”.
Hydrolysed.
GTP fills the spot on the receptor active G protein, the signal is transduced, and an ________ dephsophorylates the GTP to produce GDP.
Inactivator protein
Conformation of the G protein is altered by _______.
GTP/GDP binding.
________ (GDP-bound) G protein is capable of interacting with upstream effector proteins.
Inactive
______ (GTP-bound) G protein is capable of interacting with downstream effector proteins.
Active
The downstream effector (often an enzyme) produces ______.
Secondary messager molecules.
What is the role of secondary messengers?
Secondary messengers carry and amplify the signals from receptors (via G-protiens) to the effector molecules.
Describe the characteristics of secondary messengers.
- Short lived molecules
- Diffuse rapidly
- Allow enzymatic amplification
Which of the following are water-soluble: Ca2+ ions, DAG, NO, cAMP, cGMP, IP3.
Ca2+ ions, cAMP, cGMP, IP3
Which of the following are lipid-soluble: Ca2+ ions, DAG, NO, cAMP, cGMP, IP3.
DAG, NO
What is the function of 3’,5’-Cyclic AMP (cAMP)
Activates protein kinase A (PKA).
What is the function of 3’,5’-Cyclic GMP (cGMP)
Activates protein kinase G and opens cation channels in rod cells.
What is the function of 1,2-Diacylglycerol (DAG)
Activates protein kinase C
What is the role of Inositol 1,4,5-trisphosphate (IP3)
Opens the Ca2+ channels in the endoplasmic reticulum
What happens when adenylyl class is activated by a stimulatory hormone and the G protein complex is activated by GDP?
cAMP is released.
Describe the amplification of epinephrine down to the resulting product.
Epinephrine –> Adenylyl cyclase –> cAMP –> Protein kinase A –> Activated enzyme –> Product
