Cell Signalling Flashcards
Cells require multiple signals to (3)
-survive
-grow and divide
-differentiate
Cell signals are conveyed by ___ which control (3)
Extra-cellular signalling molecules
-which signalling molecule is released
-when and what concentration
-how it will be interpreted by the target cells
3 stages of cell signalling
- Reception
- Transduction
- Response
Signalling molecules bind to
Cellular receptors, typically on the cell surface (but can also be in the cytoplasm or nucleus)
Binding of a signalling molecule to a cellular receptor results in
A conformational change in the receptor which triggers a series of actions along a Signal Transduction Pathway leading to a specific cellular response
A ligand is
A signalling molecule
4 types of ligands are
-growth factors
-hormones
-cytokines
-chemical mediators (toxins)
Which three systems have the same signalling molecules, allowing for cooperation/integration
-endocrine
-immune
-nervous
Signalling molecules work to (4)
-activate
-inhibit
-stimulate
-suppress
Most signalling molecules are ___ and thus
-water soluble
-too large to pass through the plasma membrane
Water soluble signalling molecules have to
Bind to transmembrane proteins (surface receptors)
SOME signalling molecules are ___ and thus
-lipid-soluble
-able to pass through the plasma membrane
Lipid-soluble signalling molecules bind to
Cytoplasmic or nuclear receptors
Signalling molecules can trigger a change in (3), give an example of each
-metabolism of a cell (ex. Insulin signalling through the insulin receptor
-electrical potential across the membrane of a cell (ex. Neurotransmitter signalling in neurons)
-gene expression/transcription within the nucleus (ex. Adrenaline binding to an adrenergic receptor)
7 types of signalling molecules
-hormones
-growth factors
-cytokines
-chemokines (type of cytokine)
-neurotransmitters
-neurohormones
-infectious agents
Four types of signalling include
-endocrine
-exocrine
-autocrine
-juxtacrine
Endocrine Signalling: (2)
-Ligands: hormones
-long-distance signalling via the blood
Neurotransmitters are a special form of ___ signalling
Paracrine
Paracrine Signalling (3)
-Ligands: growth factors, cytokines, chemokines, hormones
-neurotransmitters are a special form
-act locally or over sort distances via the blood or interstitial fluid
Autocrine Signalling (2)
-Ligands: cytokines and chemokines
-signalling molecules bind to receptors on the same cell (autostimulation)
Juxtacrine Signalling (3)
-also called Contact-Dependent Signalling
-Ligands: proteins attached to plasma membrane of cell
-receptors on adjacent cell
Long-distance signalling via the blood is
Endocrine signalling
Signalling modeled binding to receptors on the same cell is called
Autocrine Signalling
Signalling that acts locally/short distances via the blood/interstitial fluid is called
Paracrine Signalling
Proteins that attach to receptors on an adjacent cell is called
Juxtacrine (Contact-Dependent) Signalling
Signal Transduction is usually a
Multi- step pathway (helps to amplify and coordinate/regulate the signal)
After the ligand binds to the receptor, the receptor interacts with
Other intracellular signalling molecules
Intracellular Signalling Molecules (2)
-directly change cellular activity
-produces intermediates (second messengers) to change cellular activity
Cellular responses to signalling can result in changes to (6)
-metabolism
-growth
-differentiation
-gene expression
-secretion
-structure (cytoskeleton)
Three types of receptors
-cytoplasmic receptors
-nuclear receptors
-surface receptors (transmembrane proteins)
Receptors have a ___ for their ligand(s)
High affinity and specificity
Specificity for a ligand(s) depends on
Binding affinity between the ligand and the binding site on the receptor
The affinity between receptors and their ligands is described by the
Equilibrium Dissociation Constant (Kd)
The higher the Kd,
The weaker the binding and the lower the affinity
Ligands are classified as either ___ or ___, depending on the outcome of ligands-receptor binding
-receptor agonists
-receptor antagonists
A single receptor may bind ___, a single ligand may bind ___
-to several different ligands
-to several different receptors
Ligands that bind to a receptor and change the receptor’s activity to produce a response are called
Agonists
Antagonists are when
A ligand binds to a receptor but does NOT produce a response
Acetylcholine (ACh) is a ___ that is released from the ___
Neurotransmitter; released from the pre-synaptic terminals of neurons
In skeletal muscle, the ACh receptors are
Ion-channel receptors (aka Nicotinic Receptors)
Toxins, such as a-bungarotoxin and tubocurare,
Bind the ACh receptor with a higher affinity than ACh, blocking the binding of ACh and resulting in paralysis of the diaphragm and death
Receptors can be defined by their
Location
Majority of receptors are ___ which means they bind the ligand ___
Transmembrane Receptors; bind the ligand OUTSIDE the cell
Most ligands are
Hydrophilic
3 types of transmembrane receptors
-ion channel-linked receptors
-enzyme-linked receptors
-G protein-coupled receptors
Ion channel-linked receptors (4)
-cation and anion channels
-rapid signalling
-found in electrically excitable cells (ie. neurons)
-also called ligand gated ion channels
Ion channel-linked receptors have a
Hydrophilic central canal (pore)
The pore of ion channel-linked receptors
Opens and closes via gates that are controlled by the binding of a ligand
Majority of enzyme-linked receptors are
Protein kinases
Enzyme-linked receptors are either
Enzymes themselves OR are directly associated with the enzymes they activate
A series of protein kinases that phosphorylation each other in succession, thus amplifying the signal, is called
Kinase Cascade
A series of protein kinases that phosphorylation each other in succession, thus amplifying the signal, is called
Kinase Cascade
Kinases are
Enzymes that transfer phosphate groups from ATP to another protein
A cell’s response to a signal often involves
Activating or inactivating proteins
A common way to change the activity of a protein is through
Phosphorylation (adding a phosphate group)
A protein kinase will
Take away a phosphate group from ATP (making it into ADP) and giving it to a protein (making it a phosphorylated protein)
Receptor Tyrosine Kinases (RTKs)
transfer phosphate groups to tyrosine residues (amino acids)
Insulin receptor is an example of a
Receptor tyrosine kinase (RTK)
When signalling molecules bind to two adjacent RTKs, (3)
-they bond together (dimerise)
-phosphates are then added to the tyrosine residues on the intracellular portion of the receptors (ie. they are phosphorylated)
-signal is then transmitted to the next messenger in the cytoplasm
G Protein-coupled receptor ligands include (7)
-odours
-pheromones
-hormones
-neurotransmitters
-light E
-lipids
-sugars
Seven-Transmembrane Receptors (7TM receptors) are also called
Transmembrane (integral) proteins
7TM receptors couple to a ___
G protein
G Protein-Coupled Receptors (GPCRs) are involved in
Many diseases, such as cancer, and are a target of ~30% of medical drugs
G proteins are
Specialized proteins that bind to nucleotides Guanosine Triphosphate (GTP) and Guanosine Diphosphate (GDP)
G proteins have __ subunits called
3 subunits:
-alpha
-beta
-gamma
A subunit will bind to ___ or ___ depending on
GTP or GDP; whether the protein is active or inactive
In the absence of a signal, GDP binds and
The entire G protein-GDP complex binds to a nearby GPCR
When a signalling molecule binds to the G Protein-Coupled Receptor (3)
-the GPCR changes conformation, activation the G protein
-GTP replaces GDP
-second messengers are produced
4 types of intracellular receptor signalling
-steroid hormones
-thyroid hormones
-vitamin D3
-retinoic acid
For intracellular receptors,
The small hydrophobic signal molecule is carried via through the body via a carrier protein and then dissociate to enter the cell
Steroid Hormone Signalling (4 steps)
- Steroid hormone is transported in the blood, bound to a carrier protein, to the surface of its target cell
- The steroid dissociates from the carrier protein and enters the cell
3.a) some steroids bind to a cytoplasmic receptor which conveys them to a nucleus
3.b) some steroids do not bind to a receptor until they enter the nucleus - The steroid-receptor complex is called a Transcription factor, and by interacting with the DNA can alter the expression of specific genes
The steroid-receptor complex within the cell is called a
Transcription Factor
Transcription Factors interact with ___ to alter __
DNA; the expression of specific genes
Second messengers (3)
-small molecules and ions that relay signals received by the cell-surface receptors
-small, diffuse rapidly
-rapid spread / amplification of signal
4 types of Second Messengers and an example
-Cyclic Nucleotides (cAMP, cGMP)
-Ions (Ca2+)
-Phospholipid-Derived Molecules (inositol triphosphate)
-Gases (nitric oxide)
Caffeine enhances the action of ___ by inhibiting __
-cAMP
-the enzyme phosphodiesterase (which degrades cAMP)
cAMP is synthesized by ___ from ___
Adenyl cyclase enzyme; ATP
One molecule of adrenaline =
10,000 molecules of glucose
Calcium concentration inside the cell is ___ than outside the cell
Lower
Calcium functions as a second messenger in
G protein and Tyrosine Kinase Pathways
What can be used to treat bipolar disorder
Lithium inhibition of the Phosphoinositol Signalling Pathway (decreases IP3 and DAG)
Nitric Oxide (NO) (4)
-free radical that diffuses across cell membranes
-both hydrophilic and lipophilic
-acts in a Paracrine or autocrine manner
-important role in many physiological functions
When nitric oxide diffuses into vascular smooth muscle cells
The smooth muscle relaxes
Membrane-bound extracellular vesicles are called
Exosomes
Exosomes are generated by
All cells
Exosomes are contained
Within multivesicular bodies
Exosomes are taken up by cells via
Endocytosis
Exosomes contain (5)
-proteins
-lipids
-metabolites
-DNA
-RNA
Exosomes are associated with ___ and likely involved in ___
Pathogenesis of cancer, inflammation, neurodegeneration; cell-to-cell communication
Exosomes-mediated responses can
Promote and suppress disease progression
Exosomes can potentially be engineered to (2)
-deliver therapeutic payloads, such as chemotherapy and immune modulators
-aid in disease diagnosis through liquid biopsies
