Cell Signaling Flashcards
2 ways cells communicate
Direct communication
Though extracellular signaling molecules (neurotransmitters & hormones)
Junctions in direct cell to cell communication
Gap Junction
Adherent and tight junctions
Molecules diffuse from cytoplasm of a cell to another. Connects cell to cell and transports ions and molecules from a cell to another.
Gap junctions
Junction that’s main function is tissue organization during organ development and remodeling.
Hold tissues together.
Adherent and tight junction
Type of signaling molecules that require direct contact for a response to occur.
Juxtacrine/contact-dependent signaling molecule
Example of contact dependent molecule
Immune cells
Signaling molecules that attaches to nearby target cell.
Paracrine
Signaling molecule that produce signal for itself.
Autocrine
Signaling molecules that attaches to distant target cells via bloodstream.
Endocrine
Special signaling molecules of nervous system. Aids in contraction of muscles.
Synaptic molecules
When a signaling mol. And receptor binds, it changes the intracellular signaling = affects target cells and its function. T/F
T
Signaling molecules are NOT static. T/F
T because it can be sensitized or desensitized
6 steps of signaling molecules
RTT - MRT
Signaling molecule binds to specific receptor
Recognition
Specific signaling molecule will attach to & cause reaction in specific
receptor proteins
Recognition
Extracellular signal is transformed into an intracellular signal (
Transduction
Aka second messanger
Intracellular signal
First messanger
Ligand
Intracellular signal & second messengers are transmitted to effector/target proteins
Transmission
Effector protein is enhanced/modified, usually by kinases/phosphatases
Modulation
Kinases
add phosphate to protein: phosphorylation
Enzyme that remove phosphate from protein: dephosphorylation
Phosphatase
Summation & integration of input from multiple pathways
Response
○ Involves feedback mechanisms that may act at any level of signaling
pathway
Termination
Signaling does not proceed indefinitely. It has to stop sometime. T/F
T
Transduces chemical signal into electrical signal
Membrane/cell surface receptors
LIGAND-GATED ION CHANNELS
AKA “seven-transmembrane receptors” or “serpentine receptors” d/t
crossing membrane 7x
G-PROTEIN COUPLED RECEPTORS
GPCRs are coupled to _____________ proteins (w/ 3 sub-units: alpha,
beta, gamma)
Heterotrimeric G protein
G protein + GTP = active or inactive
Active
G protein w/o GTP = active or inactive
Inactive
Problems and solutions of using GPCR
Problems
○ Too unstable to isolate & purify 📋
○ Lose their highly organized structure & activity once removed from cell
Solutions
Stabilize recepto gcpr (STAR)
How does star solve the problem of GPCR?
Increases its thermostability
Receptors that function as enzymes or are directly associated with
enzymes:
ENZYME-LINKED RECEPTORS
Acted on mainly by hydrophobic molecules (e.g. steroid hormones, thyroid
hormones, vitamin D)
NUCLEAR RECEPTORS
Where can NUCLEAR RECEPTORS be found?
Cytoplasm and nucleus
multiple pathways simultaneously interacting is possible. T/F
T
one signaling molecule can cause many intracellular events
Amplification:
due to interacting/network of pathways
Integration
signals can modify what happens in signal transduction pathway
Downregulation/Desensitization:
Scaffolding protein
helps keep enzymes together in one place
Bifurcate proteins
for signal to go to different pathways
Ions can become a secondary messenger. T/F
T
Ca2+ regulates many physiological processes. T/F
T
GTPases is activated by what enzyme
GAP (GTPases activating protein)
GTPases is deactivated by what enzyme
GEF (Guanine nucleotide exchange protein)
GAP activates GTP hydrolysis. T/F
T
More GAP promotes _______ G proteins.
Inactivation
More GEF _________ G proteins
Activates
2 types of G protein
Monomeric
Heterotrimeric
5 families of monomeric
Ras, rho, rab, ran, arf
Central to many enzyme-linked receptor pathways
Monomeric G proteins
Regulate multiple cell functions:
→Cytoskeletal organization
→Vesicular transport
→Gene expression
→Apoptosis
Monomeric G proteins
■ Coupled to GPCR (serpentine receptors)
■ Composed of 3 subunits α, β, & γ
Heterotrimeric G proteins
converts ATP to cyclic AMP (cAMP)
G proteins and Adenylyl Cyclase:
cAMP activates _______
Protein kinase A (PKA)
Function of PKA
activate cAMP response element-binding protein (CREB
Acts as an effector protein in the cytosol
converts phosphatidylinositol bisphosphate (PIP2) to inositol triphosphate (IP3) & diacylglycerol (DAG)
G protein and phospholipase C
activates a Ca2+ channel in endoplasmic reticulum
IP3
DAG activates ________
PKC
releases arachidonic acid from membrane phospholipids
Phospholipase A2
Arachidonic acid can be further converted to ________
Eicosanoids (prostaglandins, thromboxanes, & leukotrienes)
breaks down cAMP & cGMP to AMP & GMP
○ Helps reverse or terminate action of cAMP & cGMP
G protein and Phosphodeisterases
it converts GTP to cGMP which will perform other functions inside cell
Enzyme linked Receptor: Receptor Guanine cyclase
ANP receptor, NO receptor
Guanine cyclase receptor
Ligand binds to Type II subunit, which phosphorylates Type I subunit
Receptor Serine/Threonine Kinases
TGF-β receptor (Transforming growth factor)
Receptor Serine/Threonine Kinases:
Nerve Growth Factor (NGF) receptors, Insulin receptors
Receptor Tyrosine Kinases (RTKs):
Steps in RTKs
2 ligand bind to receptor
Dimerization
Autophosphorylation
Activated Ras + kinases = MAP
MAP alters gene expression
Some RTKs are tetrameric (e.g. insulin receptor). T/F
T
No intrinsic tyrosine kinase activity but closely associated with tyrosine
kinases
Tyrosine Kinase-Associated Receptors:
JAKS will phosphorylate ___________, which will move to nucleus to affect gene expression
STAT
Act toaffect gene transcription allowing Tyrosine Kinase-Associated
Receptors to alter gene transcription
Signal transducers and activators of transcription (STAT)
Dephosphorylates tyrosine residues phosphorylated by tyrosine kinase
Receptor Tyrosine Phosphatases:
Example of RTP
CD45 protein
Examples of TKAR
Cytokine receptor, Growth hormone receptor
What receptor is MAP located
RTK
What receptor is JAk and STAT located
TKAR
Receptors found intracellularly
Nuclear receptors may also suppress or enhance transcription
Nuclear receptor
early primary response
30 mins
delayed secondary response
Hours to days
Which of the five mechanisms of cell signaling sends signals to
target cells that are closeby or nearby?
a. Synaptic
b. Autocrine
c. Paracrine
d. Endocrine
C
A drug that is designed to bind to an intracellular receptor would
most likely have this effect:
a. Activate G proteins
b. Convert ATP to cAMP
c. Alter gene transcription
d. Open ion channels
C
Which of the following occurs as part of the G protein &
phospholipase C pathway?
a. Conversion of cAMP to AMP and cGMP to GMP
b. Activation of protein kinase C and a Ca2+ channel by DAG and IP3 respectively
c. Activation of PIP2 by IP3 to phosphorylate protein kinaseA
d. Stimulation of gene transcription by cAMP response
element binding protein
B
Associate the following molecules with its signal transduction
pathway:
Calcium
G protein and phospholipase C ; IP3
Associate the following molecules with its signal transduction
pathway:
RAS & MAP
Enzyme linked; RTK
Associate the following molecules with its signal transduction
pathway:
JAK-STAT
Enzyme linked; TKAR
Associate the following molecules with its signal transduction
pathway:
DAG & IP3
G protein and phospholipase C
Associate the following molecules with its signal transduction
pathway:
PKC
GCPR; phospholipase C; DAG
Associate the following molecules with its signal transduction
pathway:
CREB
GPCR; Adenylyl cyclase; PKA
An inflammatory response that involves cytokines and steroid
hormones was initiated. Which of the following events would most
likely occur in the cell due to these ligands?
a. Alteration of gene transcription by MAPK and cAMP response element binding protein
b. Signal propagation due to opening of Na+ channels andCa2+ channels
c. Signal propagation due to dissociation of the G α, from
the G βγ complex
d. Alteration of gene transcription by STAT and
hormone-receptor complexes
D
A receptor that activates the Ras protein can most likely be
classified under which type of receptor?
a. Enzyme-linked receptor
b. Nuclear receptor
c. G-protein coupled receptor
d. Ligand-gated ion channe
A
Which of the following occurs as part of the tyrosine kinase-associated receptor pathway?
a. Translocation of MAP kinase to the nucleus to stimulate gene transcription
b. STAT proteins phosphorylate JAKs, which will activate PKA and MAP kinase
c. Janus kinases phosphorylate STAT proteins, which then affect gene transcription
d. MAP kinases activate Ras and Raf, which will cause receptor dimerization
e. Receptor dimerization, leading to activation of enzymes that generate cGMP
C
What receptor type are MasR and AT1R?
a. Ligand-gated ion channel
b. GPCR
c. Enzyme-linked
d. Nuclear
B
IL-6 binds to which type of receptor?
a. Ligand-gated ion channel
b. GPCR
c. Enzyme-linked
d. Nuclear
C
AT1R is associated with Phospholipase C. What is part of its
mechanism of action?
a. Activate phosphodiesterases
b. Increase Ca2+ and activate PKC
c. Increase cAMP and activate PKA
d. Increase IP3 and decrease DAG
e. Release arachidonic acid
B
IL-6 binds to which type of enzyme-linked receptor?
a. Receptor guanylyl cyclase
b. Receptor serine/threonine kinase
c. Receptor tyrosine kinase
d. Tyrosine-kinase associated receptor
e. Receptor tyrosine phosphatase
D
Which statement is FALSE about cell signaling?
a. Different signaling pathways may interact with each other.
b. Signaling molecules and receptors exhibit specificity.
c. Kinases and phosphatases alter protein function.
d. “Transduction” refers to the alteration of gene expression.
e. No answer
D
Purpose of pathways
Amplification
Regulation
Specific & coordinated response
