Chapter 10: Signaling Flashcards
What are the general features of signaling pathways?
- A ligand carrying a signal binds specifically to a receptor bound to the cell membrane
- Their interaction triggers some kind of response inside the cell
- This is known as signal transduction
- Ligand does not enter the cell,
but the information is transmitted
Examples of extracellular signals
Extracellular signals can take many forms, including amino acids and their derivatives, peptides, lipids, and other small molecules. Some are formally called hormones, which are substances produced in one tissue that affect the functions of other tissues, but many signals go by other names. Keep in mind that other stimuli—such as light, mechanical stress, odorants, and tastants
What is the meaning of Kd?
Biochemists express the strength of receptor-ligand binding as a dissociation constant, Kd, which is the reciprocal of the association constant.
How to calculate Kd?
Signaling molecules behave much like enzyme substrates: They bind to their receptors with high affinity, reflecting the structural and electronic complementarity between each ligand and its binding site.
What is the interpretation of receptor-ligand binding plot?
As the ligand concentration [ L ] increases, more receptor molecules bind ligand. Consequently, the fraction of receptors that have bound ligand [ R x L ] approaches 1.0. [ R ]T is the total concentration of receptors. The dissociation constant Kd is the ligand concentration at which half of the receptor molecules have bound ligand.
Define agonists and antagonists and provide examples
- An Agonist binds to receptors and elicits a biological effect
- An Antagonist binds to the receptor but does not trigger a response
What is going on in the tyrosine kinase signaling pathway? What are the kinases?
A receptor, also a transmembrane protein, becomes activated as a kinase as a result of ligand binding. A kinase is an enzyme that transfers a phosphoryl group from ATP to another molecule.
What is going on in the tyrosine kinase signaling pathway? What is the ligand of the pathway?
The ligands are growth factor, hormones, etc.
Ligand binding to a receptor tyrosine kinase activates the kinase activity of the receptor so that intracellular proteins become phosphorylated. A series of kinase reactions activates or inhibits target proteins by adding phosphoryl groups to them.
What is going on in the G protein signaling pathway? Ligands of pathway?
Ligand binding to a G protein coupled receptor triggers the activation of a G protein, which then activates an enzyme that produces a second messenger. Second messenger molecules diffuse away to activate or inhibit the activity of target proteins in the cell.
What is going on in the G protein signaling pathway? What is the receptor of pathway?
G protein signaling pathways
* Responsible for transducing the
majority of extracellular signals
* Involves G protein-coupled receptors (GPCR)
* GPCR are known as 7TM receptors
* 7TM = 7 transmembrane helices
What is the G protein cycle in the G protein signaling pathway?
What is the role of Adenylate cyclase in the G protein signaling pathway?
Adenylate cyclase is a membrane-associated enzyme that, when activated by the GTP-bound alpha subunit, catalyzes the synthesis of the second messenger cAMP from molecules of ATP.
What is the second messenger of the G protein signaling pathway and its role?
Cyclic AMP (cAMP) is the
second messenger. cAMP functions as an allosteric activator of the kinase, and the level of cAMP determines the level of activity of protein kinase A (PKA) regulated by phosphorylation.
KINASES catalyze the phosphorylation of other proteins
What is the composition of protein kinase A?
The backbone of the catalytic subunit is light green, with its activation loop dark green. The phospho-Thr residue (right side) and ATP (left side) are shown in stick form. A peptide that mimics a target protein is blue.
What is the activation of protein kinase A?
cAMP is an allosteric activator of PKA
How is a pathway switched off?
Signaling pathways can be switched off
* By reversing the phosphorylations catalyzed by protein kinase A
* This is accomplished by
protein phosphatases
* By removing the second messenger, cAMP
Which protein side chains does PKA transfer a phosphoryl group from ATP to?
PKA transfers a phosphoryl group from ATP to the serine or threonine side chain of a target protein.
PKA is known as a Ser/Thr kinase
What is β2-adrenergic receptor an example of?
GPCR (G protein-coupled receptors)
What type of ligands are Epinephrine and Norepinephrine?
Ligands of the β2-adrenergic receptor.
Which subunits of PKA block the active sites when it is inactive?
The two regulatory subunits (R) block the active sites of the two catalytic subunits (C)
