Chapter 16 Flashcards
Signaling molecules are
Diverse
What kind of hormone diffuse through the plasma membrane and bind to
intracellular receptors located in the cytoplasm
Steroid
cannot pass through the plasma membrane and instead bind to cell surface receptors
Amino acids, peptides, and proteins
can produce different effects in different cells by
using different receptors and intracellular pathways
Acetylcholine
Cortex matters in…
Cell signaling
Fast signal response occur with changes in the…
Activity of an Intracellular profein
Slow signal responses occur in changes in…
Transcription/translation (need time for protein synthesis)
The location of a receptor depends on the
Nature of signal
Hydrophilic signals bind to
Cell surface receptors
Hydrophobic signals cross the __ and bind ___ receptors
Hydrophobic, Intracellular
Hydrophobic hormones are derivatives of
Cholesterol or tyrosine
With steroid hormone signaling the receptor may be in the
Cytoplasm or nucleus
If cytoplasmic, hormone
binding stimulates
movement to
Nucleus
Steroid hormone signaling regulates…
Transcription of target genes
a stress hormone secreted by the adrenal gland
that stimulates metabolism in many target tissues & also
suppresses the immune system
Cortisol
sex hormone secreted by the ovary that induces and maintains secondary female sexual characteristics
Estrogen
sex hormone secreted by the testis that induces and maintains secondary male sexual characteristics
Testosterone
The androgen receptor (AR) binds
Testosterone
The AR gene is located on the __ chromosome
X
Dissolved gases also cross the plasma membrane directly via
Diffusion
made in endothelial cells
diffuses into smooth
muscle cells
Nitric oxide (NO)
Induces smooth muscle relaxation
NO
Nerve releases
Acetylcholine
binds to a receptor on
the surface of an endothelial cell and stimulates synthesis
and release of NO
Acetylcholine
NO diffuses into a neighboring
Smooth muscle cell
Once NO diffuses into neighboring smooth muscle cells where it
Binds guanylyl cyclase and induces smooth muscle relaxation
Guanylyl cyclase converts
GTP to cGMP
relaxes smooth muscle
cGMP
Role of cGMP phosphodiesterase
degrades cGMP to end the signal
blocks cGMP phosphodiesterase, prolongs relaxation of smooth muscle, promotes dilation of blood vessels
Viagra
Hydrophilic signals bind
cell-surface receptors
How many classes of receptors
3
What are the classes of cell surface receptors
- Ion channel coupled receptor
- G protein coupled receptors
- Enzyme coupled receptor
Ion channel or ligand gated coupled receptors convert a
Chemical signal into electrical
have seven transmembrane alpha-helices
GPCRs
activates a membrane-bound G-protein
Ligand binding
Activated G-protein __ a target protein
activates (or inhibits)
Large and widespread receptor family (>700 in humans)
G-protein-coupled receptors (GPCRs)
Prominent in multi-cellular organisms
Enzyme-coupled receptors
Drugs can mimic signaling molecules __ block their action
or
Intracellular signaling pathways convert a
Extracellular signal to Intracellular
Roles of Intracellular signaling pathways…
Relay, amplify, integrate, distribute
sometimes using a scaffold protein to hold multiple components close together
Intracellular signaling pathways
Modulate response by regulating the activity of upstream components
(feedback)
Intracellular signaling pathways
can adjust the response to an extracellular signal
Feedbac k regulation
can produce sophisticated responses to signals
Feedback regulation
How to turn signals on and off?
- Protein phosphorylation and dephosphorylation
- GDP/GTP exchange and GTP hydrolysis
Protein phosphorylation and dephosphorylation requires what two proteins and what modification
two proteins, a kinase and phosphatase and covalent modification of the target protein
Involves non-covalent binding
GDP/GTP exchange and GTP hydrolysis
The GTPase activity of the GTP-binding protein functions as a
Timer
relay messages from G-protein-coupled receptors
Trimeric GTP-binding proteins (a.k.a. G-proteins)
help other cell-surface receptors relay signals
Monomeric GTPases
Protein kinases transfer a phosphate from ATP onto
a protein. T or F
True
A GTP-binding protein exchanges its bound GDP for
GTP to become activated.
True or false
True
Phosphatases remove the phosphate from GTP on
GTP-binding proteins, turning them off. True or false
False
Example of contact-dependent
signaling
Delta-Notch signaling
seen in several developmental
signaling pathways
Regulated proteolysis
Participates in cell specialization and differentiation
Delta noTch signaling
Nerve cell expresses
Delta
-stimulates cleavage of receptor
-fragment goes to nucleus
-Stimulates transcription
Delta-Notch signaling
To function, all extracellular signal molecules must be transported by their receptor across the plasma membrane into the cytosol.
True or false
False
cell-surface receptor capable of binding only one type of signal molecule can mediate only one kind of cell response.
True or false
False
Extracellular signal molecules that are hydrophilic must bind to a cell- surface receptor so as to signal a target cell to change its behavior.
True or False
True
Heart muscle cells, salivary gland cells, and skeletal muscle cells all express an acetylcholine receptor that belongs to the transmitter-gated ion channel family.
True or False
False
Active acetylcholine receptors on salivary gland cells and heart muscle cells activate the same intracellular signaling pathway. True or False
False
Four modes of signaling:
Endocrine, paracrine, neuronal, contact dependent
Acetylcholine bonds heart muscle cells, slowing down heart rate
True or false
True
When an extracellular signal molecule binds to a GPCR, the
GPCR undergoes a conformational change that enables it to bind
and activate a
heterotrimeric G protein
Some G proteins activate membrane-bound enzymes such as
Adenylyl cyclase (generates cAMP)
Phospholipase C (generates IP3 and diacylglycerol)
the cAMP mediates what kind of responses
fast and slow responses
The phospholipase C pathway triggers a rise in
cytosolic Ca2+
__ signal triggers many biological processes
Ca2+
GPCRs consist of __ polypeptide chain that crosses the
membrane as __ a-helices
single, 7
Heterotrimeric G proteins (a.k.a. large G proteins) contain __ subunits
3
Alpha and gamma subunits are __ bound to membrane lipids
covalently
Alpha subunit with bound GDP is
Alpha subunit with bound GTP is
inactive
active
GTP hydrolysis by the a
subunit __
of the G protein
terminates activation
alpha subunit with GTP activates (or
inhibits) a target protein for
as long as they remain in contact
Many activated G proteins target
membrane-bound enzymes
Activated alpha subunit stimulates
adenylyl cyclase
Adenyl cyclase converts
ATP to cAMP, an important 2nd messenger
adenyl cyclase is an example of a ___; multiple cAMP
molecules are produced by a single adenylyl cyclase
signal amplification
cAMP phosphodiesterase converts
cAMP to AMP to terminate the signal
What inhibits cAMP
phosphodiesterase, prolongs cAMP
signaling in the nervous system
Caffeine
Epinephrine binds to a class of GPCRs called
adrenergic receptors
Some act via cAMP
– Increase heart rate
– Promote fat breakdown in fat cells, glycogen breakdown in skeletal
muscle
Epinenphrine=adrenaline
True or False
(1) A constitutively active mutant form
of PKA increases the amount of
phosphorylated phosphorylase
kinase
(2) A constitutively active mutant form
of PKA decreases the affinity of
epinephrine for the GPCR
(3) A constitutively active mutant form
of PKA increases the amount of
cAMP produced by adenylyl
cyclase
true
false
false
active PKA enters the nucleus, where it…
phosphorylates specific transcription factors
This is one way to convert a brief
signal into a long-term response
PKA/cAMP
cleaves an inositol phospholipid to generate watersoluble IP3 and membrane-bound diacylglycerol
Phospholipase C
What opens Ca2+ channels in ER membrane and increases cytoplasmic Ca2+
IP3
What recruits & activate PKC (protein kinase C)
Diacylglycerol & Ca2+
phosphorylates many target proteins
protein kinase A
Most widespread and common calcium binding proteins in the cytosol
calmodulin (CaM)
CaM (calmoduln) activates how many targets
several
Calmodulin activates how many binding sites on the alpha helix
2
One major target that calmodulin binds and activates to is
CaM-kinase
Role of CaM-kinase
phosphorylates target proteins
How do you terminate a Ca2+ signal
Use the Ca2+ ATPase pump to lower
the cytosolic concentration of Ca2+
Enzyme-coupled receptors either act as
enzymes or form complexes with other proteins that act as enzymes
Receptor tyrosine kinases contain an
intracellular tyrosine kinase domain
recruit a complex of intracellular signaling proteins
Activated RTKs
Most RTKs activate the…
Ras
Some RTKs activate PI 3-Kinase to produce…
lipid docking sites for the activation of other enzymes
Binding of a signal molecule induces
receptor dimerization
What stimulates kinase activity & trans-autophosphorylation (each receptor phosphorylates the other) of tyrosines
receptor dimerization
Each phosphorylated tyrosine recruits a
specific adaptor protein
Specific adapter proteins recruited by phosphorylated tyrosines couple…
RTKs to other signaling molecules
a monomeric GTPase that is anchored to the membrane
Ras
Active RTK recruits proteins (including Ras-GEF) that stimulate __
Ras to exchange its __ for __
inactive, GDP for GTP
Ras-GTP activates many __ targets
downstream
How to terminate Ras activation
GTP hydrolysis is stimulated by Ras-GAP
RTK and Ras signals are __-lived, but activation of the __ converts short signals into longer signals
short, MAP kinase pathway
What kinase can act on cytoskeleton, metabolism, gene expression, etc
MAP Kinase
Activating Ras mutations are found in
cancer
In activating Ras mutations, when can you turn off the signal
Cannot turn off signaling, even in the absence of signal
phosphorylates inositol phospholipids
PI 3-kinase
After PI 3-kinase phosphorylates inositol phospholipids, following phosphorylation these lipids recruit __ signaling molecules, including….
intracellular, Protein Kinase 1 and Akt kinase (PKB)
Activated Akt kinase promotes
cell survival and growth
A growth factor stimulates the proliferation of cultured cells. The receptor that binds this growth factor is a receptor tyrosine kinase (RTK), and many tumor cell lines have mutations in the gene that encodes this receptor. Would the following mutations be expected to promote or inhibit uncontrolled cell proliferation?
(a) A mutation that destroys the kinase activity of the receptor
(b) A mutation that enables the receptor to dimerize in the absence of a signal
molecule
(c) A mutation that inactivates the protein tyrosine phosphatase that normally
removes the phosphates from tyrosines on the activated receptor
(d) A mutation that prevents the binding of the growth factor to the receptor
A. Inhibit
B. promote
C. Promote
D. Inhibit
Where does cross talk occur between GPCR and RTK pathways?
phospholiase C activation, Ca2+ signaling, phosphorylation of downstream targets
Protein Kinase A (PKA) doesn’t effect anything __
upstream before activated
