Chapter 13.3

Question 1

G-protein-coupled receptors contain … and undergo … when a hormone binds

Answer 1

seven membrane-spanning helices; conformational changes

Question 2

agonist binding to a G-protein-coupled receptor induces the alpha subunit of the associated heterotrimeric G protein to exchange … for … and dissociate from the beta and gamma subunits

Answer 2

GDP; GTP

Question 3

… is activated to produce cAMP, which in turn activates protein kinase A

Answer 3

adenylate cyclase

Question 4

signaling activity is limiting through the action of … that act on cAMP and cGMP

Answer 4

phosphodiesterases

Question 5

…: proteins that are members of the superfamily of regulatory GTPases known as G proteins which bind the guanine nucleotides GTP and GDP and hydrolyze GTP

Answer 5

heterotrimeric G proteins

Question 6

the monomeric G proteins are essential for:
…
…
the growth of …
… (as ribosomal accessory factors)
… (as components of the signal recognition particle and the SRP receptor)

Answer 6

signal transduction 
vesicle trafficking
actin microfilaments
translation 
protein targeting

Question 7

(components of heterotrimeric G proteins) …: transmembrane proteins that bind their corresponding agonist on their extracellular side, which induces a conformational change on their cytoplasmic side

Answer 7

G-protein-coupled-receptors

Question 8

(components of heterotrimeric G proteins) heterotrimeric G proteins, which are anchored to the … side of the plasma membrane and which are activated by a GPCR when it binds its corresponding agonist

Answer 8

cytoplasmic

Question 9

(components of heterotrimeric G proteins) …: a transmembrane enzyme that is activated (or in some cases inhibited) by activated heterotrimeric G proteins

Answer 9

adenylate cyclase

Question 10

activated AC (adenylate cyclase) catalyzes the synthesis of … (…) from ATP

Answer 10

adenosine-3’-5’-cyclic monophosphate (cAMP)

Question 11

cAMP is a …: that is, it intracellularly transmits the signal originated by the extracellular ligand

Answer 11

second messenger

Question 12

GPCRs have essential … functions, constituting the olfactory and gustatory receptors, as well as the several light sensing proteins in the retina, which are known as …

Answer 12

sensory; rhodopsins

Question 13

the GPCRs are all … membrane proteins with 7 transmembrane alpha helices of generally uniform size: 20-27 residues. their .. and … segments vary in length. these are the portions that participate in binding ligands and heterotrimeric G proteins

Answer 13

integral; N- and C- terminal segments

Question 14

Many GPCRs are modified by n-glycosylation and/or by the palmitoylation of a cys residue, so they are also …

Answer 14

lipid-linked glycoproteins

Question 15

by alternating between two discrete conformations, one with … bound and one without, the GPCR receptor can transmit an extracellular signal to the cell interior

Answer 15

agonist

Question 16

…: G proteins that consist of an alpha, beta, and gamma subunit

Answer 16

heterotrimeric G proteins

Question 17

the large alpha subunit of the heterotrimeric G protein consists of two domains connected by polypeptide linkers:

1. a highly conserved … domain structurally similar to those in monomeric G proteins such as Ras, and is known as a … domain
2. a … domain unique to them

Answer 17

GTPase; Ras-like; helical

Question 18

the beta subunit of the heterotrimeric G proteins consists of an N-terminal helical domain and a C-terminal domain comprising 7 4-stranded antiparallel beta sheets, called a …

Answer 18

beta propeller

Question 19

in its unactivated state, a hetertrimeric G protein maintains its heterotrimeric state and its Galpha subunit binds GDP. however, the binding of a Galpha * GDP-Gbeta,gamma complex to its cognate GPCR in complex with an agonist induces the galpha subunit to exchange its bound … for …

Answer 19

GDP; GTP

Question 20

when gtp is bound to Galpha, its gamma phosphoryl group promotes conformational changes in three of Galpha’s so called …, causing Galpha to dissociate from Gbeta,gamma –> activation of the G protein
GTP hydrolysis reassembles the inactive form

Answer 20

switch regions

Question 21

one of the major targets of the heterotrimeric G protein system is the enzyme …, which the binding of GTP to Galpha activates.

Answer 21

adenylate cyclase

Question 22

…: stimulatory G protein

Answer 22

Gsalpha

Question 23

inhibitory G proteins:

Answer 23

Gialpha

Question 24

bc a single agonist-receptor interaction can activate more than one G protein, this step of the signal transduction pathway serves to … the original extracellular signal

Answer 24

amplify

Question 25

cells can adjust their ... levels in response to a great variety of stimuli

Answer 25

cAMP

Question 26

cAMP is a polar, freely diffusing second messenger. in eukaryotic cells, its main target is ... (PKA; also known as ... or cAPK), an enzyme that phosphorylates specific Ser/Thr residues of numerous cellular proteins

Answer 26

protein kinase A; cAMP-dependent protein kinase

Question 27

the intracellular concentration of cAMP determines the fraction of PKA in its ... form and thus the rate at which it .. its substrates

Answer 27

active; phosphorylates

Question 28

the phosphoryl group at PKA's Thr 197 functions to ... its active site residues

Answer 28

properly orient

Question 29

The R subunit of protein kinase A

Answer 29

competitively inhibits its C subunit

Question 30

The R subunit contains two homologus cAMP-binding domains, Ra and Rb, and a so-called ..., which blocks substrate binding

Answer 30

autoinhibitory segment

Question 31

each step of a signal transduction pathway can potentially be regulated, so the nature and magnitude of the cellular response ultimately reflect the presence and degree of ... or ... of all the preceding components of the pathway

Answer 31

activation; inhibition

Question 32

many drugs and toxins exert their effects by modifying components of the ... system

Answer 32

adenylate cyclase

Question 33

a hallmark of biological signaling systems is that they adapt to long-term stimuli by reducing their response to them, a process named ... These signaling systems therefore respond to ... levels rather than to their absolute values

Answer 33

desensitization; changes in stimulation

Question 34

active PKA phosphorylates ..., which in turn, phosphorylates several intracellular Ser and Thr residues on the C-terminus of the hormone-receptor complex but not on the receptor alone. the phosphorylated receptor binds proteins known as ... to form complexes that sterically block the formation of the receptor-Gs complex, resulting in desensitization

Answer 34

beta-adrenergic receptor kinase; beta-arrestins

Question 35

in any chemically based signaling system, the signal molecule must eventually be eliminated in order to control the .. and ... off the signal and to prevent interference with the reception of ..

Answer 35

amplitude; duration; subsequent signals

Question 36

in the case of cAMP, this second messenger is hydrolyzed to AMP by enzymes known as ...

Answer 36

cAMP-phosphodiesterases

Question 37

The PDE superfamily, which includes both cAMP-PDEs and ... is encoded in mammals by at least 20 different genes grouped into 12 families

Answer 37

cGMP-PDEs

Question 38

PDEs may be activated by one/more of a variety of agents, including a calcium ion and phosphorylation by PKA and ...

Answer 38

insulin-stimulated protein kinase

Question 39

PDEs provide a means for crosstalk between ... and those using other types of signals

Answer 39

cAMP-based signaling systems