ch.17 Flashcards
In terms of postal service, what is the ligand similar to?
the letter in the mail
In terms of postal service, what is the receptor similar to?
the mailbox
In terms of postal service, what is the signal transduction pathway similar to?
how you respond to the letter
In terms of postal service, what is the cell response similar to?
finalize by sending back a letter
True or False: Ligands can be hydrophobic or hydrophilic.
true
What kind of interaction does a receptor have?
cell surface or intracellular
describe direct cell-cell signaling.
proteins on the surface of the cells bind to each other
What are the 3 categories based on the distance over which signals are transmitted?
endocrine, paracrine, synaptic
describe endocrine signaling
for long distance; goes to blood; interaction between hormone and receptor is high affinity
describe paracrine signaling
molecules released by one cell act on neighboring target cells
describe autocrine signaling
cells respond to signaling molecules that they themselves produce
Which type of signaling is more precise than endocrine signaling?
synaptic signaling
Which type of signaling has rapid transmission of signals?
synaptic signaling
What are the sex steroids, produced by the gonads?
testosterone, estrogen, and progesterone
What makes cyclic GMP?
guanylyl cyclase
what binds to guanylyl cyclase?
Nitric oxide (NO)
What does cGMP induce?
muscle cell relaxation and blood vessel dilation
define second messenger
molecule that relays a signal from a receptor to a target inside the cell
cGMP is an important what?
second messenger
What happens when it is dark (in terms of cGMP)?
high levels of cGMP, cGMP binds to Na+ channels, Na+ rushes in + depolarizes the photoreceptor in the retina, Ca2+ channels open, Ca2+ leads the fusion of vesicles to release inhibitory neurotransmitters, inhibits any signals from continuing
What happens when it is light (in terms of cGMP)?
the 11-retinal changes to all trans, leads to the activation of the phosphodiesterase, GMP, Na+ is not rushing in, No vesicles releasing neurotransmitters, no longer inhibit vision
acetylcholine causes what?
skeletal muscle contraction + causes heart cells to relax
Are neurotransmitters hydrophobic or hydrophilic?
hydrophilic
Many neurotransmitter receptors are ________
ligand-gated ion channels
Enkephalins and endorphins act as what?
neurotransmitters and as neurohormones
define neurohormones
natural analgesics that decrease pain responses
What binds to morphine receptors on brain cells?
neurohormones
What do nerve growth factors (NGF) regulate?
development and survival of neurons
What do epidermal growth factors (EGF) do?
stimulates cell proliferation
When are platelet-derived growth factors (PDGF) released?
during blood clotting at the site of the wound
What do PDGFs stimulate?
proliferation of fibroblasts, contributing to regrowth of the damaged tissue
what are fibroblasts important for?
making the connective tissue that all the cells grow on
what do cytokines regulate?
development and differentiation of blood clots + activities of lymphocytes during the immune response
membrane-anchored growth factors remain where?
within the plasma membrane
what’s the function membrane-anchored growth factors?
signaling molecules in direct cell-cell interactions
Most ligands responsible for cell-cell signaling bind where?
surface receptors on target cells
what does intracellular signal transduction regulate?
surface receptors regulate intracellular enzymes
What do intracellular enzymes do?
transmit signals from the receptor to a series of additional intracellular targets
What is the largest family of cell surface receptors?
G protein-coupled receptors
How many times do the G protein-coupled receptors pass through the membrane (spanning alpha helices)?
7
In G protein-coupled receptors, how are signals transmitted?
guanine nucleotide-binding proteins (G proteins/GTPases)
What are the 3 subunits of the large G protein?
alpha, beta, and gamma
define heterotrimeric G proteins?
distinguishes large G proteins from other guanine nucleotide-binding proteins
The regulator G protein signal encourages what?
to chop off the terminal phosphate (acts like a GAP)
What do G proteins connect?
receptors to distinct targets (also regulate ion channels)
______ _____ cells have acetylcholine receptors that are G protein-coupled.
Heart muscle
The alpha subunit of the G protein in heart muscle cells (Gi) does what?
inhibits adenylyl cyclase
The beta-gamma subunits in heart muscle cells does what?
opens K+ channels in the plasma membrane
What slows heart muscle contraction?
when beta-gamma subunits open K+ channels in the plasma membrane
What is the role of cAMP as a second messenger?
signals the breakdown of glycogen to glucose in muscle cells
How is cAMP formed?
from ATP by adenylyl cyclase
how is cAMP degraded to AMP?
by cAMP phosphodiesterase
What is cAMP mediated by?
cAMP-dependent protein kinase or protein kinase A (PKA)
Glycogen metabolism PKA phosphorylates how many enzymes?
2
Describe signal amplification.
binding of a hormone molecule leads to activation of many intracellular target enzymes
Each receptor may activate up to 100 molecules of ____
Gs
In many animal cells, cAMP activates what?
transcription of genes that have a regulatory sequence called cAMP response element (CRE)
Free catalytic subunit of protein kinase A goes to the nucleus and phosphorylates transcription factor______ ______.
CREB (CRE-binding protein)
Phosphorylation of CREB leads to what?
recruitment of coactivators and expression of cAMP-inducible genes
When is the target protein active?
When protein kinase A phosphorylates ATP (to add a phosphate to the target protein)
Odorant receptors are _____________
G protein-coupled
What stimulates adenylyl cyclase?
second messengers
The opening of Na+ channels in the plasma membrane leads to what?
the initiation of a nerve impulse
Many cell surface receptors are directly linked to what?
intracellular enzymes
What is the largest family of intracellular enzymes?
tyrosine kinases
Most polypeptide growth factors work through what receptors?
receptor tyrosine kinases
The human genome encodes how many receptor tyrosine kinases?
58
Which terminus is the ligand-binding domain in receptor tyrosine kinases?
N-terminus
Which terminus domain is the tyrosine kinase domain in receptor tyrosine kinases?
C-terminus
Describe the receptor tyrosine kinases steps.
growth factor binds –> dimerize –> auto phosphorylate
What are the 2 roles of autophosphorylation?
1) phosphorylation of tyrosine in the catalytic domain
2) phosphorylation of tyrosine outside the catalytic domain
Phosphorylation of tyrosine in the catalytic domain does what?
increases protein kinase activity
Phosphorylation of tyrosine outside the catalytic domain creates what?
binding sites for other proteins that transmit signals downstream from the activated receptors
What are the 4 signaling molecule domains?
1) Src Homology 2 (SH2)
2) Phosphotyrosine binding (PTB)
3) Src homology 3 (SH3)
4) pleckstrin homology (PH)
Which of the 4 signaling molecule domains bind to phosphorylated tyrosine?
SH2 + PTB
Which of the 4 signaling molecule domains bind to proline rich regions?
SH3
nonreceptor tyrosine kinases stimulate what?
intracellular tyrosine kinases with which they are noncovalently associated
cytokine receptor superfamily includes what?
receptors for most cytokines and some polypeptide hormones
Janus kinase (JAK) family
kinases associated with cytokine receptors
What are key targets of JAK kinases?
STAT proteins
STAT proteins are what?
transcription factors with SH2 domains
STAT proteins are inactive in the cytosol until what?
cytokine receptors are stimulated
What can JAK phosphorylate?
JAK, receptor, STAT
Once STAT proteins are phosphorylated, what happens?
the STAT proteins dimerize and translocate to the nucleus
MAP kinase pathway is what?
a cascade of protein kinases found in all eukaryotic cells
what do MAP kinases do?
mitogens activate mitosis
MAP kinases involve what amino acid kinases?`
serine + threonine kinases
MAP kinases first found in mammalian cells belong to the ____.
ERK family (extracellular signal-regulated kinase)
ERK signaling emerged from the studies of what?
Ras proteins
Ras proteins are activated by what?
GEFs (guanine nucleotide exchange factors)
What do GEFs stimulate the exchange of?
GDP for GTP
Ras-GTP activity is terminated by what?
GTP hydrolysis –> stimulated by interaction of Ras-GTP with GAPs
Some activated ERK goes to the nucleus, where it does what?
regulates transcription factors by phosphorylation
_____ and ______ cells have multiple MAP kinase pathways
yeast and mammalian
Each cascade consists of 3 protein kinases…
terminal MAP kinase + 2 upstream kinases
What do mammalian MAP kinases include?
ERK, JNK, and p38 kinases
Specificity of MAP kinase signaling is maintained partly by what?
physical association on scaffold proteins
PI 3-kinase/Akt pathway is based on what?
a second messenger derived from the membrane phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2)
What is PIP2 phosphorylated by?
phosphatidylinositide (PI) 3-kinase
What is PI 3-kinase recruited to?
activated receptor tyrosine kinases via its SH2 domain
PIP3 targets a _______/________ kinase called Akt via its pleckstrin homology (PH) domain.
serine/threonine
What is Akt phosphorylated and activated by?
PDK1
Activation of Akt also requires phosphorylation by protein kinase _______, which is also stimulated by growth factors.
mTORC2
Akt phosphorylates several target proteins such as what?
transcription factors (FOXO)
Akt phosphorylation of FOXO sequesters it in ______ form in the cytosol.
inactive
The mTORC1 complex is activated ______ of Akt.
downstream
what does mTORC1 regulate?
cell size by controlling protein synthesis
mTORC1 also inhibits _______ ________ by regulating autophagy.
protein degradation
What happens in the phospholipase C/calcium pathway?
hydrolysis of PIP2 by phospholipase c
what are the 2 second messengers that phospholipase c produces?
DAG and IP3
where is DAG located?
remains associated with the plasma membrane
what does DAG activate?
serine/threonine kinases of the protein kinase c family
what does IP3 bind to?
receptors that are ligand-gated Ca2+ channels in the ER
What is one of the major Ca2+ binding proteins that mediates the effects of Ca2+
calmodulin
when is calmodulin activated?
when Ca2+ concentration increases
members of the ______ kinase family are also activated by Ca2+/calmodulin.
CaM
One form of CaM kinase regulates what?
synthesis and release of neurotransmitters
In the TGF-B/Smad pathway, receptors for transforming growth factor B (TGF-B) directily phosphorylate transcription factors of the _____ family.
Smad
Wnt proteins are what?
Growth factors that bind to receptors of the Frizzled and LRP families
signaling from frizzled and LRP leads to what?
stabilization of β-catenin, a transcriptional activator
