Chapter 16 - Part II - Cell Signaling Flashcards
Many actions trigger an increase in intracellular Ca2+ concentrations. a) sperm fertilization an egg cell = ? b) nerves signaling muscle cells = ? c) secretory cells (including neurons) = ?
a) development b) contraction c) secretion
Ca2+ can trigger biological effects because an unstimulated cell has an extremely ____ concentration of free Ca2+ in the cytosol, compared with its concentration in the ___ space and in the ____, creating a steep electrochemical gradient.
low (10^-7M); extracellular 10^-3M; ER
Ca2+ binds and affects the action of ____ proteins like _____.
Ca2+ responsive ; calmodulin
Calmodulin activates ______.
CaM-kinases (Ca2+/Calmodulin dependent protein kinases)
Calmodulin has a dumbbell shape, with 2 globular ends connected by a long alpha helix. Each end has ____ Ca2+-binding domains. Conformational changes in Ca2+/calmodulin that occur when it binds to an isolated segment of a target protein. In this conformation, the ___ helix jackknifes to surround the target.
2; alpha
PKA, PKC, CaM-kinases phosphorylate selected signaling and effector proteins on ___ and ___, thereby altering their activity.
serines; threonines
Different cell types contain different sets of signaling and effector proteins and are therefore affected in different ways. True or false?
True
GPRC signaling allows for signal ____.
amplification
An example of GPRC signaling that allows for signal amplification is __.
Rod photoreceptor cells
In the rod photoreceptor cells example, the a) signal = ? b) GPRC = ? c) G-protein = ?
a) light; b) rhodopsin; c) transducin
_____ results in the closure of cation channels and a voltage change. Signal is then relayed to the ____.
Signaling cascade; brain
Enzyme-coupled receptors often regulate ___, ____, ____ and/or ___.
cell growth; proliferation; differentiation; survival
In enzyme-coupled receptors, responses are typically ___, and their effects may require many intracellular transduction steps that usually lead to a change in _____.
slow; gene expression
Enzyme-coupled receptors require less steps than GPCR. True or false?
False. It requires more steps.
What does RTKs stand for?
Receptor tyrosine kinases
RTKs are 7 transmembrane.
False. RTKs are single transmembrane.
RTKs are single transmembrane.
true
Signal binding to RTKs occur in ___ space.
extracellular
Two RTKs __ after signal binding.
dimerize
Dimerized RTKs ___ each other.
phosphorylate
Intracellular signaling proteins are ___ upon binding to the phosphorylated RTKs.
activated
Signaling is turned off when _____ dephosphorylates the RTKs.
protein tyrosine phosphates
RTKs are ____ protein that attach _____. And they are also ____.
membrane; phosphates; enzymes
Activated RTKs recruit a ___ of intracellular signaling ___.
complex; proteins
Mutations in receptor _____ are frequently associated with the human cancer.
Tyrosine kinase
Abnormalities in signaling via RTKs have a major role in the development of most ____.
cancers
The enzyme that removes phosphates is ________.
phosphatase.
These phosphorylated tyrosines attract different intracellular signaling proteins (as many as __ or __ different), which then become activated and pass on the signal.
10; 20
Typically, the binding of a signal molecule to the extracellular domain of a receptor tyrosine kinases (RTK) causes two receptor molecules to associate into a ____. The signal molecule is itself a ___ and thus can physically cross-link two receptor molecules; other signal molecules induce a conformational change in the RTKs, causing the receptors to dimerize, too.
dimer; dimer;
In either case, ____ brings the kinase domains of each systolic receptor tail into contact with the other; this activates the kinases to ___ the adjacent tail on several ____. Each phosorylated tyrosine serves as a specific docking site for a different intracellular signaling protein, which then helps relay the signal to the cell’s interior.
dimer formation; phosphorylate; tyrosine
What 3 intracellular signaling molecules are activated by RTKs?
1- phospholipase C 2- Ras 3- phosphoinositide 3-kinase
What generates DAG and IP3?
phospholipase C
What monomeric GTPase is attached to the plasma membrane?
Ras
What phosphorylates inositol phospholipids?
phosphoinositide 3-kinase (PI 3-kianse)
__ is activated when a signal binds a RTK leading to the activation of ___.
Ras; Ras-GEF
Most RTKs activate the Monomeric GTPase called ___, and then signaling molecule binding.
Ras
___ helps activate the GTP binding protein by promoting its binding to GTP.
GEF
An adaptor protein docks on a particular phosphotyrosine on the activated receptor. The adaptor recruits a Ras guanine nucleotide exchange factor ____ that stimulates Ras to exchange its bound GDP for GTP.
Ras-GEF
These monomeric GTP-binding proteins are aided by two sets of regulatory proteins. ___ activate the switch proteins by promoting the exchange of GDP for GTP. And ___ turn them off by promoting GTP hydrolysis.
GEFs; GAPs
If Ras contains a mutation that leads to a defect in GTP hydrolysis, this could fuel uncontrolled proliferation in cancer because…
Ras is able to signal to downstream pathways inappropriately
Activated Ras initiates the ___ signaling module.
MAP
Activated Ras protein initiates the ___ which activates a 3-kinase signaling module, which relays the signal. The final kinase in the module, ____, phosphorylates various downstream signaling or effector proteins.
MAP kinase signaling module; MAP kinase
RTKs are usually activated by - signa;-induced _____; - which allows the receptors to ____ themselves and ___ intracellular signaling proteins that are stimulated by the phosphorylated receptor.
dimerization; phosphorylate; activate
After it is activated, the receptor is dephosphorylated, and thereby inactivated, by a _____.
protein tyrosine phosphatase
A mutation in the gene that encodes the protein tyrosine phosphatase will in appropriately increase the activity of the receptor and promote _________.
uncontrolled cell profileration
A mutation that inactivates the protein tyrosine phosphatase that normally removes the phosphates from tyrosines on the activated receptor promote _____.
uncontrolled cell proliferation
Many tumor cell lines have mutations in the gene that encodes receptor tyrosine (RTK). Which of the following types of mutations would be expected to promote uncontrolled cell proliferation?
a mutation that inactivates the protein tyrosine phosphatase that normally removes the phosphates from tyrosine on the activated receptor.
RTKs are usually activated by signal-induced ________; which allows the receptors to ____ themselves and activate intracellular signaling proteins that are stimulated by the phosphorylated receptor.
dimerization; phosphorylate
____ is often mutated in cancerous cells.
Ras
About 30% of human cancers contain mutations in the __ gene.
Ras
You examine a cell line with a constitutively active Ras protein that is always signaling. Which of the following conditions will turn off signaling in this cell line?
addition of a drug that blocks protein Y from interacting with its target
The Ras protein is always on. True or False?
True
Ras protein activates Y protein. And the Y protein sends the signal. True or false?
True
If you block the active signaling protein X, does that turn off the signaling in this cell line?
No.
If you add a drug that prevents protein X from activating Ras, would that turn off signaling in this cell line?
No. Active Ras protein is ALWAYS on. There will be no effect.
Will the addition of a drug that increases the affinity of protein Y and Ras turn off signaling in this cell line?
No. You’re trying to turn off signaling. Increasing the affinity of Y will only increase signaling.
____ generates phosporylated inositol phospholipid upon RTK activation.
PI 3-kinase
PI 3-kinase generates ____ upon RTK activation.
phosphorylated inositol phospholipid
What are docks for proteins (like protein kinase 1 and Akt) that bind and become activated? (Think… what is kinase? when you think of 1, what do you think of? where are they going to bind?)
phosphorylated inositol phospholipid
RTKs activate the PI-3-kinase-Akt signaling pathway. An extracellular survival signal, such as IGF, activates an RTK, which recruits and activates _____. This enzyme then phosphorylates an ___ that is embedded in the cytosolic side of the plasma membrane. The resulting phosphorylated inositol phospholipid then attracts intracellular signaling proteins that have a special domain that recognizes it.
PI-3 kinase; inositol phospholipid
One of these signaling proteins, ____, is a protein kinase that is activated at the membrane by phosphorylation mediated by two other protein kinases (here called protein kinases 1 and 2); protein kinase 1 is also recruited by the phosphorylated lipid docking sites. Once activated, ____ is released from the plasma membrane and phosphorylates various downstream proteins on specific serines and threonines.
AKT; AKT;
Phosphorylation by ___ inactivates proteins that promote cell death.
Akt
In phosphorylation by Akt, ___ is the cell-death protein.
Bcl2
Overall, Akt ___ cell survival.
promotes
Phosphorylation of Bad ____ active Bcl2.
releases
Activated Akt promotes cell survival. One way it does so is by phosphorylating and inactivating a protein called ___. In its unphosphorylated state, ____ promotes apoptosis (a form of cell death) by binding to and inhibiting a protein called Bcl2 which otherwise suppresses apoptosis.
Bad; Bad
When Bad is phosphorylated by Akt, Bad releases _____, which now blocks apoptosis, thereby promoting _____.
Bcl2; cell survival
Which of the following statements is false?
d
Phosphorylation by indirectly activates ___, a kinase, which _____ cell growth.
Tor; promotes
___, a cancer drug, inactivates Tor.
Rapamycin
Akt stimulates cells to grow in size by activating the serine/threonine kinase Tor. The binding of a growth factor to an RTK activates the ____ signaling pathway. Akt then indirectly activates Tor by phosphorylating and inhibiting a protein that helps to keep Tor shut down. Tor stimulates protein synthesis and inhibits protein degradation by phosphorylating key proteins in these processes. The anticancer drug ___ slows cell growth by inhibiting Tor. In fact, the Tor protein derives its name from the fact that is is a target of ____.
Akt; rapamycin; rapamycin
In plants, there are RTKs, steroid hormone nuclear receptors, cAMP, and few GPCRs.
False. There are No RTKs, steroid hormone nuclear receptors, cAMP, and few GPCRs.
Plants have lots of serine-threonine kinases. True or False?
True
In plants, signal binding to an ____ relives transcriptional repression in plants.
ethylene receptor
The ethylene response in plants involves:
+ a ___ transmembrane receptor;
+ when the receptor is not bound to ____;
+ the receptor activates a _____.
dimeric; ethylene; protein kinase
The ethylene response in plants involves:
+ when the receptor is not bound to ethylene;
+ the receptor activates a protein kinase,
+ which activates an intracellular pathway;
+ that leads to a degradation of a ________ important for transcribing the ethylene-responsive genes;
+ So transcriptional ____ occurs in plants.
transcriptional regulator;
repression
Signaling pathways are highly interconnected. True or false?
True
So activation of the GPCR depends on what protein?
G protein or
monomeric GTPase (eg. Ras protein.)
Intracellular signaling proteins can ___ incoming signals.
integrate
A protein kinase can act as an integrating device in signaling if it ______.
is activated by 2+ proteins in different signaling pathways.
Calcium ion release triggers all of the following biological processes EXCEPT
action potential transmission along an axon.
Shown is a schematic of the light-induced signaling cascade in rod photoreceptor cells. At which step(s) does the response become amplified so that one photon stimulates a multifaceted response?
cyclic GMP phosphodiesterase hydrolyzing cGMP molecules
Protein kinase is an enzyme that functions in which of the following ways?
activates or inactivates other proteins by adding a phosphate group to them
What role do phosphatases play in signal transduction pathways?
They inactivate protein kinases to turn off signal transduction.
Consider this pathway:
epinephrine → G protein-coupled receptor → G protein → adenylyl cyclase → cAMP
The second messenger in this pathway is ________.
cAMP
A mutation that knocks out the GTPase activity of a G protein would have what effect on a cell?
The G protein would always be active.
The activation of receptor tyrosine kinases is characterized by
dimerization and phosphorylation.
Many tumor cell lines have mutations in the gene that encodes receptor tyrosine kinase (RTK). Which of the following types of mutation would be expected to promote uncontrolled cell proliferation?
a mutation that inactivates the protein tyrosine phosphatase that normally removes the phosphates from tyrosines on the activated receptor
Shown below is a diagram of how theoretical intracellular signaling pathways could integrate incoming signals to produce a coordinated cell response. Which signal(s) would lead to activation of both kinase 1 and kinase 2?
signals A and D
Enzymes that degrade cAMP.
cyclic AMP phosphodiesterase
Communication system where the signaling molecule is affecting the secreting cell itself ___________________
autocrine
