Cell Signaling Flashcards
Are all hormones hydrophobic?
no
some like peptide-hormones are hydrophilic and have a hard time passing the cell membrane
Signal transduction
any process by which a cell converts one kind of signal or stimulus into another
sequence of linked reactions by enzymes within the cell
accomplished through secondary messengers
Secondary messengers
molecules that relay signals received at receptors on the cell surface to target molecules in the cytosol/nucleus
amplify the strength of the signal
Example of signal amplification
lots of cAMP secondary molecules are created through one ligand molecule of epinephrine
Categories of secondary messengers
cyclic nucleotides (ex: cAMP), ions, and lipids
anything but proteins
Two classes of extracellular molecules? Which one is larger class?
- Intracellular receptors
2. Extracellular receptors (larger class)
What types of extracellular molecules trigger intracellular receptors?
small and hydrophobic molecules can move through the plasma membrane
ex: steroid hormones (cortisol) and nitric oxide
What types of extracellular molecules trigger extracellular receptors?
signals that are too hydrophilic to cross the plasma membrane
ex: insulin
What controls blood pressure?
degree of contraction of smooth muscle is important for blood flow and controls BP
What types of cells line every blood vessel?
endothelial cells
Where is nitric oxide produced?
endothelial cells from arginine
What does NO trigger?
moves from endothelial cells to smooth muscle and activates guanylyl cyclase
Guanylyl cyclase
stimulates formation of cGMP which triggers relaxation of smooth muscle
Phosphodiesterase
PDE
within smooth muscle tissues, breaks down cGMP and causes the smooth muscle to constrict
Viagra
inhibits PDE and results in prolonged cGMP signaling and prolonged relaxation
Steroid hormones
hydrophobic hormones that bind to receptors in the cytoplasm or nucleus
these complexes then act as promoting factor to regulate gene transcription
Cortisol example
example of a steroid hormone that forms a complex that supresses the immune system
3 types of extracellular receptor models
G-protein linked receptors
Ion-channel linked receptors
Enzyme linked receptors
G-protein linked receptors overview
several different types of G-proteins that each bind a specific type of receptor and set of downstream targets
all G-proteins have alpha, beta, gamma subunits and operate similarly
What is the largest family of extracellular receptor models?
g-protein linked receptors
trimeric G-proteins
alpha, beta, gamma subunits of g-protein
Inactive G-proteins
bound by GDP at the alpha-subunit
What happens when a hydrophilic signal binds to the extracellular receptor?
shape change on the cytoplasmic side of the membrane that allows a g-protein to bind to the receptor
What happens when a g-protein binds to the receptor?
alpha-subunit swaps GDP nucleotide to GTP to activate the g-protein
Does the alpha-subunit catalyze the swap of GDP to GTP?
NO
What happens when the g-protein is activated?
alpha subunit can detatch from beta and gamma subunits
g-protein can move around the cell and roam plasma membrane
activated alpha and beta-gamma subunits can interact directly with target proteins in the plasma membrane to trigger amplification
How do alpha and beta-gamma subunits become unactivated?
alpha-subunit hydrolyses the bound GTP to GDP
alpha subunit rejoins with the beta-gamma subunit and becomes inactive
Cholera
caused by inability to hydolysize GTP to GDP
*review how to treat this on a molecular level
What does Gs type of g-protein activate?
Adenylyl cyclase
Adenylyl cyclase
catalyzes cAMP formation
cAMP
secondary messenger that activates the enzyme Protein Kinase A
PKA phosphorylates specific gene transcription facts which then trigger specific gene expression
What degrades cAMP?
phosphodiesterase
caffeine inhibits phosphodiesterase
What does Gq type of g-protein activate?
Phospholipase C
activates through phosphylation from the alpha-subunit
Phospholipase C
hydrolyses phospholipid, PIP2 into IP3 and DAG
DAG = lipid tails
IP3=soluble sugar
DAG
comes from hydrolysis of PIP2
secondary messenger that moves around plasma membrane
DAG works with calcium to activate PKC
IP3
comes from hydrolysis of PIP2
moves into cystoplasm, since soluble, and binds to calcium channels on the smooth ER
Why are calcium channels on the smooth ER?
calcium deposits are stored there
What happens when IP3 binds to calcium channels?
the channels allow calcium to diffuse from the smooth ER to the cytoplasm
Calcium
once released from the smooth ER, acts as a secondary messenger with DAG to activate PKC
Ion-channel linked receptors
convert chemical signals into electrical signals
can be opened to let certain ions in or out of a cell and are responsible for rapid transmission of signals across synapses in the nervous system
example of ion-channel linked receptors
Acetylcholine is a neurotransmitter that opens up acetylcholine receptor to Na+ ions
makes the inside of cell have positive charge
example of enzyme linked receptor
Epidermal Growth Factor Receptor (EGFR)
What happens when EGF signal molecule binds to EGFR?
it triggers dimerization
what happens once receptors are dimerized?
Tyrosin Kinase phosphylates attached tyrosines on the cytosolic tail
Why is the phosphorylation of EGFR trans-?
left-hand kinase phosphorylates right-hand tyrosines and vice versa
What binds to the phospho-tyrosine residues?
downstream cytoplasmic proteins
What do downstream cytoplasmic proteins do?
build a bridge between the receptor tyrosine kinase (RTK) and the Ras protein, which is subsequently activated
Ras protein
small protein bound by a lipid tail to the internal plasma membrane
RAS protein is a single subunit GTP-binding protein
Ras protein activates a phosphorylation cascade in which a series of protein kinases phosphorylate and activate one another (MAPKKK -> MAPK)
How is the Ras protein activated?
by exchange of GDP to GTP
What is the last protein that the Ras- protein stimulates?
MAP-kinase
MAP kinase
phosphorylates regulatory proteins on serine and theronine
leads to growth (epidermal GROWTH factor receptor)
Mutant Ras proteins
unable to dissociate GTP and are always activated
leads to cancer because promotes unregulated growth
what is meant by the term “always on?”
indicates that an enzyme is on regardless of what is happening before it
for example, it can bypass phosphorylzation step
means that to reduce its effects you have to turn off DOWNSTREAM constituents
Are signaling pathways independent of one another?
No
there is often crosstalk between pathways
How is cell response to extracellular signals determined?
Determined by the total number of signals that the cell can interpret
autrocrine
self signaling
juxtacrine
signaling touching cells
paracrine
signaling nearby cells
endocrine
signaling cells far away through the bloodstream
