Test 4

10000

Typically the concentration of calcium ions in intracellular stores is ____________ fold higher than in the cytosol.

B

Typically, when a ligand binds its cognate receptor: A.a protein component at the top of the pathway is inactivated intracellularly B.a protein component at the top of the pathway is activated intracellularly C.a protein component at the bottom of the pathway is activated intracellularly D.a protein component at the middle of the pathway is activated intracellularly E.a protein component at the top of the pathway is activated extracellularly

C and D

Under the same conditions that lead cultured normal cells to exhibit decreased growth rates, what happens to malignant cells? Select the two most appropriate answers.​ a)They continue to grow and divide.​ b)They pile on top of one another forming clumps.​ c)Their growth rates decrease.​ d)They fail to respond to the types of signals that cause normal cells to cease growth and division​

B

What allows receptors for extracellular signaling molecules present on the responding cell's surface to recognize such molecules so readily? a) They bind the signaling molecules with low affinity. b) They bind the signaling molecules with high affinity. c) They denature the signaling molecules. d) They stabilize the signaling molecules. e) They infiltrate the signaling molecules.

C

What does telomerase do? a) It maintains centromeres at chromosome ends (telomeres), thus allowing cells to continue to divide.​ b) It degrades centromeres at the telomeres of chromosomes, thus allowing cells to continue to divide.​ c) It maintains telomeres at the ends of chromosomes, thus allowing cells to continue to divide.​ d) It degrades telomeres at the ends of chromosomes, thus allowing cells to continue to divide.​ e) It maintains telomeres at the ends of chromosomes, thus preventing cells from continuing to divide.​

D

What happens if a G 1 cell sustains genetic damage?​ a) The p53 protein concentration rises very rapidly.​ b) There is no increased expression of the p53 gene.​ c) The p53 protein exhibits an increase in stability.​ d) a, b, and c​ e) a and b​

B

What happens quite often to the number of normal receptors in the plasma membranes of malignant cells as compared to normal cells?​ a) Malignant cells usually have the same number of receptors in their plasma membranes as normal cells.​ b) Malignant cells usually have a much larger number of plasma membrane receptors than normal cells.​ c) Malignant cells usually have a much smaller number of plasma membrane receptors than normal cells.​ d) Malignant cells usually have no plasma membrane receptors, while normal cells have them.​ e) None of these are correct​

D

What mechanism of the following explains receptor mediated dimerization? A.Ligand binding causes allosteric. B.inhibition of the receptors leading to dimer disintegration C.Ligands act enzymatically to cause receptor dimerization D.Ligand binding causes allosteric regulation of the receptors leading to dimerization E.Ligand binding causes allosteric inhibition of the receptors leading to dimerization F.none of the choices

B

What part of the cell cycle does the pRB protein help to regulate? a) the S - G 2 transition b) the G 1 - S transition c) the G 2 - M transition d) the G 0 - G 1 transition e) the M - G 2 transition

D

What would happen if cultured cells to a tumor lacking a functional RB gene if it was reintroduced with a wild-type copy of the gene into those cells? a)The cells immediately die b)The cancer phenotype remains c)The cancer phenotype is more extreme d)The cancer phenotype disappears

A

When can tumor cells undergo apoptosis if they have sustained damage to DNA? a)if they have a functioning TP53 gene b)if they have a non-functioning BAX gene c)if they have a functioning RP gene d)if they have a non-functioning TP53 gene e)if they have a non-functioning RP gene

withdrawl from the cell cycle

When cells are exposed to stressful situations such as damaging radiation or to harmful chemicals, what response does the MAP Kinase pathway coordinate?

D

When conformational shift in the alpha subunit of the G protein occurs in GPCR signaling, what is the next step? A.Increase in the affinity of the receptor for a G protein on the cytoplasmic surface of the membrane B.Binding of GTP by the G protein G protein binds to activated receptor forming a receptor-G protein complex C.Binding of a hormone or neurotransmitter to a G-protein coupled receptor D.The G protein releases the GDP

Gs family

Which family of the heterotrimeric G-proteins function by activating adenylyl cyclase? A.Gs family B.G12/13 family C.Gr family D.Gi family E.Gq family

A

Which family of the heterotrimeric G-proteins function by inhibiting adenylyl cyclase? A.Gi family B.Gs family C.G12/13 family D.Gq family E.none of the choices

all are correct

Which of the following is/are likely to be true when a normal G 1 cell sustains genetic damage? -There is no increased expression (transcription) of the p53 gene -None is correct -All are correct -The p53 protein concentration rises very rapidly -The p53 protein exhibits an increase in stability

C

Which one of the following steps terminate the signaling from the G-alpha subunit? A.The G alpha subunit releases GDP and binds GTP. B.The bound GTP is hydrolyzed to GMP. C.The bound GTP is hydrolyzed to GDP. D.The bound GDP is phosphorylated to GTP.

Malignant and normal cells grow and divide at similar rates

Which statement below is a proper statement based on several experiments, about the abilities of normal cells and cancer cells to grow and divide when cultured under conditions favorable for cell proliferation?

seven alpha-helical transmembrane domains

Why are GPCRs called as 7-TM (transmembrane) receptors?

C

Why can cancer cells proliferate in the absence of serum? a) Their nuclei depend on these serum growth factors to maintain their structure. b) The serum inhibits their growth, while it is necessary for normal cells. c) The cell cycle of cancer cells does not depend on signals transmitted from serum growth-factor receptors located at their surface. d) The cell cycle of cancer cells depends on signals transmitted from serum growth-factor receptors located in their cytoplasm. e) Their mitochondria depend on serum growth factors for their activity.

B

Wild type version of proteins such as Src and Ras (mutant forms of which are often involved in cancers) are: a)Integral membrane proteins b)Lipid-anchored proteins c)Peripheral membrane proteins d)None is correct e)all are correct

B

You are studying two rodent cell lines, one malignant and one normal. You carry out an experiment in which you fuse malignant and normal cells. What happens?​ a) All of the hybrid (fused) cells behave like malignant cancer cells.​ b) Some of the hybrid cells lose malignant traits.​ c) Some of the hybrid cells gained more extreme malignant traits.​ d) Most of the hybrids died shortly after fusion.​ e) The hybrids began to fuse together spontaneously making giant multinucleate cells.​

B

You culture cells and selectively block MYC gene expression. What is the effect on the cells? a) Cell progression through the cycle continues unabated. b) Cell progression through G 1 is blocked. c) The cells arrest in the middle of mitosis. d) The cells arrest in the middle of meiosis. e) The cells arrest in the middle of S phase.

A

You study two cell lines. In one, the MDM2 protein is overexpressed; in the other the p53 protein is absent. What difference would you expect in the behavior of these two cell lines? a) In cells containing overexpressed MDM2, p53 levels will be low; in cells lacking the TP53 gene, p53 levels are also low; thus there is no difference in behavior. b) In cells containing overexpressed MDM2, p53 levels will be high; in cells lacking the TP53 gene, p53 levels are low; thus there is a drastic difference in behavior. c) In cells containing overexpressed MDM2, p53 levels will be high; in cells lacking the TP53 gene, p53 levels are high; thus there is no difference. d) In cells containing overexpressed MDM2, p53 levels will be low; in cells lacking the TP53 gene, p53 levels are high; thus there is no drastic difference. e) None of these are correct.

signaling pathways

____ ____ consist of a series of proteins

target proteins

____ ____ ultimately receive a message to alter cell activity

ligands

_____ activate receptors that stimulate effectors to give rise to a physiological response

protein phosphorylation

______ _____ can change protein behavior in one of several ways

receptors

______ on or in target cells receive an extracellular message

C

__________ is an approach that tries to get the immune system more involved in the fight against cancer. a)transcranial stimulation b)neuroimmunomodulation c)Immunotherapy d)Gene therapy e)angiogenesis inhibition

E

A lack of a functional TP53 gene __________. a) causes a cell carrying damaged DNA to be destroyed b) causes a cell carrying damaged DNA to fail to be destroyed c) will allow genetically unstable cells to continue to divide d) will stop genetically unstable cells from dividing e) b and c

These cells are especially sensitive to growth factor stimulation.

A quarter of human breast cancers overexpress the HER2 gene. What is the consequence of overexpression of the encoded protein in such cancers

apoptosis, protein that normally acts to inhibit apoptosis

BCL-2 oncogene is most closely linked to which process? What is the function/role of the normal version of the BCL-2 protein expressed at normal levels?

D

Based on some experiments, cancer is thought to arise from the uncontrolled proliferation of a single wayward cell. Therefore, cancers are considered to be __________ in origin. a)global b)variant c)local d)monoclonal e)polyclonal

B

Bcl-2 behaves as a(n) ________ by promoting ___________. a)oncogene, cell division b)oncogene, survival of potential cancer cells that would otherwise die by apoptosis c)syngene, cell division d)cancer gene, survival of potential cancer cells that would otherwise die by apoptosis e)haplogene, survival of potential cancer cells that would otherwise die by apoptosis

rotation or movement of these transmembrane alpha helices causes changes in the conformation of the cytoplasmic loops this in turn leads to an increase in the affinity of the receptor for a G protein present on the cytoplasmic surface of the plasma membrane

Because the transmembrane alpha helices are attached to the cytoplasmic loops...

The cell cycle of cancer cells does not depend on signals transmitted from serum growth-factor receptors located at their surface

Explain why cancer cells may proliferate even when serum is not provided?

plasma membrane, lipid chains, alpha, gamma

G proteins are held at the ____ ___ by ____ ___ that are covalently attached to the _ and _ subunits

E

Most common oncogene in human tumors and what it encodes? a)the MYC gene, a protein kinase that enhances cell differentiation b)the RB gene, a GTP-binding protein that serves as an on-off switch for a key cell signaling pathway that controls cell proliferation c)the RAS gene, a DNA polymerase that replicates DNA for dividing cells d)the MYC gene, an RNA polymerase that transcribes mRNA encoding proteins needed for cell division e)the RAS gene, a GTP-binding protein that serves as an on-off switch for a key cell signaling pathway that controls cell proliferation

G protein-coupled receptor kinase

Phosphorylation of the GPCRs by ________ sets the stage for the binding of arrestins (complete for binding with the G proteins)

4-5-1-6-3-2

Place the following events in the proper order. 1) Dissociation of Ga from the G protein complex. 2) Activation of one or more cellular signaling proteins. 3) Production of a second messenger, like cAMP. 4) Replacement of GDP by GTP on the Ga after interaction with an activated GPCR. 5) Conformational change in the Galpha subunit causing a decreased affinity for the Gbeta & gamma subunit. 6) Galpha-subunit with its attached GTP activates an effector like adenylyl cyclase

A

The cells of a multicellular organism communicate with each other using _______ also known as ligands. A.extracellular messenger molecules B.ion transport between cells C.intracellular messenger molecules D.electrical signals between cells E.mainly ATP

A and D

The fact that tumor cells depend, in many cases, on glycolysis may reflect ________. Select the two most appropriate answers. a)the high metabolic requirements of cancer cells b)the low metabolic rate of cancer cells c)the high oxygen levels the cancer cells usually encounter d)an inadequate blood supply within the tumor

C

The following happens when a G-protein-coupled receptor activates a G protein. a)The beta subunit exchanges its bound GDP for GTP b)The GDP bound to the alpha subunit is phosphorylated to form bound GTP c)The alpha subunit exchanges its bound GDP for GTP d)It activates the alpha subunit and inactivates the beta-gamma complex

B

The growth factor RGF stimulates proliferation of cultured rat cells. The receptor that binds RGF is a receptor tyrosine kinase called RGFR. Which of the following types of alteration would be most likely to prevent receptor dimerization? a)A mutation that increases the affinity of RGFR for RGF b)A mutation that prevents RGFR from binding RGF c)Changing tyrosine's that are normally phosphorylated on RGFR dimerization to alanine's d)Changing tyrosine's that are normally phosphorylated on RGFR dimerization to glutamic acid's

D

The length of time a G protein will signal is determined by _____. a)The activity of phosphatases that turn off G proteins by dephosphorylating G-alpha b)The activity of phosphatases that turn GTP into GDP c)The degradation of the G protein after G-alpha separates from G-beta-gamma d)The GTPase activity of G-alpha

its loss of growth hormone

The most important property of a cancer cell in vivo as well as in vitro is :

the G1-S transition

The pRB protein, helps regulate which phase of the cell cycle?

the Gα subunit dissociates from the Gβγ complex and binds to an effector (in this case adenylyl cyclase), activating the effector. The Gβγ dimer may also bind to an effector (not shown), such as an ion channel or an enzyme.

explain step 3

activated adenylyl cyclase produces cyclic AMP, or cAMP.

explain step 4

the GTPase activity of Gα hydrolyzes the bound GTP, deactivating Gα.

explain step 5

Gα reassociates with Gβγ, reforming the trimeric G protein, and the effector ceases its activity.

explain step 6

the receptor has been phosphorylated by a G protein-coupled receptor kinase (GRK)

explain step 7

in step 8 the phosphorylated receptor has been bound by an arrestin molecule, which inhibits the ligand-bound receptor from activating additional G proteins. The receptor bound to arrestin is likely to be taken up by endocytosis."

explain step 8

conformational change

hormone binding results in a ____ ____ that causes the hormome-receptor complex to move into the nucleus and bind to elements present in the promoters or enhancers of hormone-responsive genes

causes the receptor to assume an active conformation that requires rotations and shifts of the transmembrane alpha helices relative to eachother

how does ligand binding disturbs receptor interactions

sensitive, resensitized

if receptors are recycled and returned to the cell surface the cells remain (unsensitive/sensitive) to the ligand and are said to be _____

activating or inactivating an enzyme increasing or decreasing protein-protein interactions changing the subcellular location of the protein triggering protein degradation

in what ways can protein phosphorylation change protein behavior

Each receptor subunit phosphorylates its partner on tyrosine residues found in regions adjacent to the kinase domain.

once activated, the kinase domain of receptor tyrosine kinases do what?

messenger molecules travel short distances through extracellular space this model is currently being modified/cytoneme hypothesis

paracrine

phosphorylation

protein conformation is usually altered by _____

function as ligand-regulated transcription factors diffuse across the plasma membrane and bind to their receptors (which are present in the cytoplasm)

steroid hormone receptors function

noncovalent interactions, transmembrane alpha helices

the inactive conformation of the GPCR is stabilized by ____ ___ between specific residues in the _____ _ ____

desensitized

upon arrestin binding to GPCRs become ____

G protein-coupled receptors

what are GPCRs

receptor protein-tyrosine kinases

what are RTKs

"a small family of proteins that bind to GPCRs and compete for binding with heterotrimeric G proteins." "binding prevents the further activation of additional G proteins."

what are arrestins

Hormones (both plant and animal) Neurotransmitters Opium derivatives, Chemoattractants (odorants, tastants,) Photons

what are some natural ligands that bind to GPCRs

ligand

what binds to the receptor

autocrine

what cell signaling system is A

paracrine

what cell signaling system is B

endocrine

what cell signaling system is C

represent a second class of receptors that have evolved to translate the presence of extracellular messanger molecules into changes inside the cell

what do RTKs do

translate the binding of extracellular signaling molecules into the activation of GTP-binding proteins

what do the alpha receptors in GPCRs do

cyclic AMP (CAMP)

what does adenyly cyclase produce

second messenger

what is CAMP

arrestin-bound GPCRs are internalized when they are trapped in clathrin-coated pits that bud into the cytoplasm

what is happening in step 2

"clathrin-coated buds are transformed into clathrin-coated vesicles that deliver their contents, including the GPCRs, to endosomes. When present in the endosomes, arrestins can serve as scaffolds for the assembly of signaling complexes, including those that activate the MAPK cascade and the transcription factor ERK (step 3). "

what is happening in step 3

GPCRs are delievered to the lysosomes where they are degraded returned to the plasma membrane in a recycling endosome

what is happening in step 4 and in step 5

Small molecules such as amino acids and their derivatives (e.g., acetylcholine, epinephrine, dopamine). Gases such as NO and CO. Steroids, derived from cholesterol Eicosanoids, derived from arachidonic acid Various peptides and proteins

what is included in extracellular messengers

G-protein coupled receptors (GPCRs) Receptor protein-tyrosine kinases (RTKs) Ligand gated channels Steroid hormone receptors Specific receptors

what is included in receptor types

bind to extracellular ligands

what is the ability of ligand-gated channels

the structure is arrestin-bound GPCRs

what is the structure in step 1

the bound GTP is hydrolyzed to GDP

what step terminates the signaling from the G-alpha subunit

messenger molecules reach their target cells through the bloodstream

endocrine

the ligand binds to the receptor, altering its conformation and increasing its affinity for the G protein to which it binds.

explain step 1

the Gα subunit releases its GDP, which is replaced by GTP.

explain step 2

kinases, phosphatases

(kinases/phosphatases) add phosphate groups while (kinases/phosphatases) remove them

GDP, GTP

A ____ is exchanged for ___ on the Galpha subunit, thus activating it and promoting association with the effector

D

After G protein binds to activated receptor forming a receptor-G protein complex, what is the next event or consequence that occurs in GPCR signaling? A.Release of GDP by the G protein B.Binding of a hormone or neurotransmitter to a G-protein coupled receptor C.Increase in the affinity of the receptor for a G protein on the cytoplasmic surface of the membrane D.Conformational shift in the alpha subunit of the G protein E.Increase in the affinity of the receptor for a G protein on the cytoplasmic surface of the membrane

D

Angiogenesis is formation of new ____________. a)cartilage cells b)muscle fibers c)gland cells d)blood vessels e)neuronal structures

less

G12/13 members are (more/less) well characterized

off, hydrolysis, GDP

Ga subunits can turn themselves (on/off) by ____ of GTP to ____ to Pi

dissociates, binds

Galpha ____ and ____ to the effector (adenyly cyclase)

inhibiting adenyly cyclase

Gi subunits function by

contain Ga subunits that activate PLCb

Gq famly members contain what

couple receptors to adenylyl cyclase

Gs family members do what

Gs family members couple receptors to adenylyl cyclase Gq family members contain Ga subunits that activate PLCb Gi subunits function by inhibiting adenylyl cyclase G12/13 members are less well characterized

Heterotrimeric G proteins come in four varieties:

by introducing the DNA suspected of containing the oncogene into cultured cells and looking for altered growth properties

How have scientists historically identified oncogenes?

C

How will an oncogenic form of RAS that is constitutively active affect cells? a)The cells increase in volume permanently b)The cells differentiate c)The cells lose growth control d)The cells dedifferentiate e)The cells stop dividing

A

I can be phosphorylated by specific protein kinases, who am I? A.tyrosine B.valine C.alanine D.asparagine

A

In G protein-coupled receptors, GDP is exchanged for GTP on the G___subunit. A) Alpha B) Beta C) Gamma

D

In nonstimulated cells, calmodulin protein does not bind to calcium. Why? A.Calmodulin's affinity for calcium ions is too high to allow binding in an nonstimulated cell. B.In a nonstimulated cell, calcium ions are destroyed. C.In a nonstimulated cell, calcium ions are produced. D.Calmodulin's affinity for calcium ions is too low to allow binding in a nonstimulated cell. E.In a nonstimulated cell, calcium ions preferentially bind to another protein in the cytosol.

it inhibits glycogen synthase kinase 3 by phorphorylating it

Insulin signaling activates the kinase PKB that after a few steps will lead to activation of the enzyme glycogen synthase. This leads to glycogen synthesis. What does PKB do to activate glycogen synthase?

C

Insulin signaling activates the kinase PKB that after a few steps will lead to activation of the enzyme glycogen synthase. This leads to glycogen synthesis. What does PKB do to activate glycogen synthase? A.it activates Glycogen kinase by phosphorylating it B.it degrades Glycogen synthase kinase 3 by phosphorylating it, C.it inhibits Glycogen synthase kinase 3 by phosphorylating it, D.it binds allosterically to Glycogen synthase, it activates Glycogen synthase kinase 3 by phosphorylating it

C

Insulin-receptor substrate binds to tyrosine phosphorylation sites on the activated insulin receptor via ____________. A.a PKB domain B.an N-terminal PH domain C.a PTB domain D.a long tail containing tyrosine phosphorylation sites a C-terminal PH domain

phosphotyrosine

SH2 domains and PTB domains bind to ____________________ residues.

D

SH2 domains and PTB domains bind to ____________________ residues. A.phosphoserine B.Phosphothreonine C.phosphotryptophan D.phosphotyrosine E.phosphoalanine

true

T/F: Protein kinases transfer the terminal phosphate from ATP onto a protein

false

T/F: each protein in a pathway does not alter the conformation of the next protein

true

T/F: ligand binding to the receptor extracellular domain altering conformation

D

The G-protein coupled receptor amino-terminus is on the ________ of the cell, and the carboxyl-terminus is on the _______ of the cell. A)Inside, inside B)Outside, outside C)Inside, outside D)Outside, inside

the cell has receptors on its surface that respond to the messenger

autocrine