Lecture 21 - Cell Signalling and Signal Transduction Flashcards
def: produced far from the target tissues, which they reach via the circulatory system
endocrine
def: diffusible and act “locally” or over a short range. their distribution is usually limited by their inherent instability
paracrine
def: act on the same cell that produces them
autocrine
def: many of these molecules act as neurotransmitters and hormones, such as epinephrine
amino acids and their derivatives
def: cholesterol derivatives, which regulate sexual differentiation, pregnancy, carbohydrate metabolism, and ion excretion
steroids
def: fatty acids that regulate pain, inflammation, blood pressure, and blood clotting. NSAIDs block their synthesis
eicosanoids
def: a wide variety of secreted proteins act as ligands, regulating processes such as cell division, differentiation, cell death/survival and the metabolism
polypeptides and proteins
what are the 3 main classes of cell surface receptors?
- G-protein coupled receptors
- enzyme-linked receptors (RTK)
- ion channel linked receptors
what is the requirement for cells to respond to a particular ligand?
they must express the receptor that specifically recognizes and binds the messenger
receptors have ________ _______ that fits the ligand very closely
binding site
ligands bind to receptors in a highly specific way, through _____ _______ ___________-
non-covalent interactions
def: relationship between the [ligand] in solution and the number of receptors occupied
receptor affinity
def: the [free ligand] needed to produce a state in which half the receptors are occupied
dissociation constant Kd
receptors with high affinity for their ligand, have ____ Kd, and vice versa
low
def: drugs that activate the receptor they are bound to
agonists
def: drugs that bind receptors without activating it, thus preventing the naturally occurring messenger from activating the receptor
antagonists
what is isoproterenol used to treat and is it an antagonist or agonist?
- treat asthma
- agonist of the epinephrine G-protein coupled receptor on bronchial smooth muscle
what is alprenolol used to treat and is it an antagonist or agonist?
- anxiety attacks or cardiac arrhythmias
- antagonist that blocks the affect of epinephrine responsive receptor on cardiac muscle cells that increases heart rate contraction, therefore slowing the patient’s heart rate
what is generally the first step of a cell signalling pathway?
extracellular ligands, called “first messengers” bind to a receptor triggering a signalling cascade
what does ligand binding induce in the transmembrane receptor protein and what does it do?
induces a conformation change in the receptor protein which acts to relay the signal across the membrane
the _________ __________ _____________ of a transmembrane receptor protein can act as or activate effector molecules
active cytoplasmic domain
def: some effectors generate small molecules or ions that relay signals from one location to another in the cell
second messengers
once proteins near the “top” of the intracellular signalling pathway are activated, what happens?
a series of protein modifications occur, in a specific sequence
each protein in the cascade acts on the subsequence protein, ________ ____ __________, leading to _______ _____ ____________ of the downstream protein
altering its conformation, activation or inhibition
what is the most common modification in proteins down the cascade?
phosphorylation
________ __________ are eventually reached, which activate a specific cellular process
target proteins
def: the ability of a cell to respond to ligand-receptor binding by altering its behaviour or gene expression
signal transduction
kinases _______
phosphates ___________
kinases phosphorylate
phosphates dephosphorylate
in addition of phosphate groups to hydroxyl groups on (most commonly) :
Serine (S), Threonine (T), Tyrosine (Y)
def: changes a proteins charge and generally leads to a conformation change which can alter ligand binding or other features of the protein resulting in an increase or decrease of it’s activity
phosphorylation
what are the 4 main stages of the cell signalling pathway?
- transfer
- modulation
- amplification
- divergence
at each step in the resulting cascade of events, a _________ __________ stimulates the production of many molecules needed for the next step
signalling intermediate
def: the multiplication of the effect of the signal
signal amplification
def: signals from one ligand + receptor can activate effectors in different pathways
divergence
def: signals from a variety of unrelated ligands/receptors can converge to activate common effectors
convergence
def: signals from different pathways can effect components of multiple pathways, passing information back and forth
crosstalk
in general, combinations of signals generate _______ and different cellular responses
crosstalk
cells are geared to sense ligand concentration ___________ rather than fixed concentrations
changes
def: when receptors are occupied for prolonged periods, the cell adapts to no longer respond to the ligand
receptor down-regulation
what are the 2 ways receptor down-regulation can be achieved ?
- cells reduce the density of receptors on their cell surface via receptor-mediated endocytosis
- cells can adapt to signals by desensitization, alterations to the receptor that lower its affinity for the ligand
def: mediate the uptake of material that will be used by the cell, receptor will deliver the bound material to the early endosome, releasing it because of the lower affinity at higher [H+], then return to the cell membrane
housekeeping receptors
def: bind extracellular messengers that change the activity of the cell, these receptors will be degraded, reducing the sensitivity of the cell to further stimulation
signalling receptors
