Signal Transduction Pathways Flashcards
What do signal transduction cascades do?
They mediate the sensing and processing of stimuli, information from the environment in the form of light,smell or blood glucose concentration. These molecular circuits detect, amplify, and integrate diverse external signals to generate responses such as changes in enzyme activity, gene expression or ion channel activity.
What is the first step of a molecular circuit?
The release of the primary messenger. A stimulus such as a wound or a digested meal triggers the release of the signal molecule, also called the primary messenger.
Why do most signal molecules pass through the cell membrane or through transporters?
Because most signal molecules are too large and too polar to pass through.
What is the second step of a molecular circuit?
The reception of the Primary Messenger. The information presented by sigma, molecules must be transmitted across the cell membrane without actually entering the cell. Membrane receptors are used to transfer information from the environment to the cell interior. The information conveyed by the receptor must be transducer into other forms of information that can alter the cells biochemistry.
What does the formation of the receptor-ligand complex alter?
The formation of the complex alters the tertiary or quaternary structure of the receptor, including the intracellular domain. However structural changes in the few receptors that are bound to ligands aren’t sufficient enough to yield a response from the cell.
What is the third step in the molecular circuit?
Relay of information by the second messenger. Structural changes in receptors lead to changes in the concentration of small molecules, called second messengers, that are used to relay information from the receptor-ligand complex.
What are prominent second messengers?
Cyclic AMP, cyclic GMP, calcium ion, IP3, DAG.
What are concenquences of using second messengers?
One is that second messengers are often free to diffuse to other compartments if the cell, such as the nucleus p, where they can influence gene expression and other processes.
Another consequence is that the signal may be amplified significantly in the generation of second messengers. Each activated receptor-ligand complex can make many second messengers within the cell.
What is the fourth step in a molecular circuit?
Activation of effectors that directly alter the physiological response. The u,Ti ate effect if the signal pathway is to activate, or inhibit, the pumps, enzymes, and gene transcription factors that directly control metabolic pathways, gene activation, and processes such as nerve transmission.
What is the fifth step in a molecular circuit?
Termination of the signal. After the signalling process has been initiated and the information has been transited to affect other cellular processes, the signalling process must be terminated.
What happens if the signal isn’t terminated?
Cells lose their responsiveness to new signals. Signalling processes that fail to be terminated properly may lead to uncontrolled cell growth and cancer.
What are the three classes that membrane receptor proteins that convey environmental information fall into?
- Seven-transmembrane-helix receptors
- Dimeric receptors that recruit protein kinases
- Dimeric receptors that are protein kinases
What signals initiate the seven-transmembrane-helix receptors (7TM) to transmit information?
Diverse signals such as photon, odorants, tastants, hormones, and neurotransmitters.
What do 7TM receptors contain and what do mutations cause?
These receptors contain seven helices that span a membrane bilayer and mutations in these receptors cause a host of diseases such as colour blindness, extreme obesity, night blindness, precocious puberty.
What is an example of a 7TM receptor and what does it bind?
β-adrenergic receptor that binds epinephrine, a hormone responsible for the fight or flight response.
How do the 7TM receptors work when a ligand binds?
The binding of a ligand on the outside of the cell induces a conformational change in the 7TM receptor that can be detected inside the cell.
What is the next step in the pathway after the binding of epinephrine by the β-adrenergic receptor?
The conformational change in the cytoplasmic domain of the receptor activated a GTP-binding protein. The signal coupling protein is termed a G protein. The activated G protein stimulates the activity of adenylate cyclase, an enzyme that increases the concentration of the second messengers cAMP by forming it from ATP.
How do the G proteins operate?
In the inactivated state, the guanyl nucleotide bound to the G protein is GDP. In this form, the G protein exists as a heterotrimer consisting of α, β, γ subunits.
What is the exchange of the bound GDP for GTP catalyzed by?
The ligand-bound receptor
WHat happens when the ligand-receptor complex interacts with the heterotrimeric G protein?
The nucleotide-binding site is opened so that the GDP can depart and GTP can bind. The a subunit simultaneously dissociates from the by dimer.
What happens when the G-protein heterotrimer dissociates into Ga and Gby units?
The signal that the receptor has bound to its ligand is transmitted.
How many genes does the human genome encode for Ga.
15 genes, one of which Gas, is expressed ubiquitously while the others are expressed in specific cell types.
True or false: A single ligand-receptor complex can stimulate nucleotide exchange in many G-protein heterotrimers.
True
Hundreds of Ga molecules aee converted to their GTP-bound forms from their GDP-bound forms for each bound molecule of hormone, giving an amplified response.
G-protein-coupled receptor
The 7MT receptors are sometimes referred to as GPCRs because all 7TM receptors appear to be coupled to G proteins.