Chapter 13.3 Flashcards
G-protein-coupled receptors contain … and undergo … when a hormone binds
seven membrane-spanning helices; conformational changes
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
GDP; GTP
… is activated to produce cAMP, which in turn activates protein kinase A
adenylate cyclase
signaling activity is limiting through the action of … that act on cAMP and cGMP
phosphodiesterases
…: 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
heterotrimeric G proteins
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)
signal transduction vesicle trafficking actin microfilaments translation protein targeting
(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
G-protein-coupled-receptors
(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
cytoplasmic
(components of heterotrimeric G proteins) …: a transmembrane enzyme that is activated (or in some cases inhibited) by activated heterotrimeric G proteins
adenylate cyclase
activated AC (adenylate cyclase) catalyzes the synthesis of … (…) from ATP
adenosine-3’-5’-cyclic monophosphate (cAMP)
cAMP is a …: that is, it intracellularly transmits the signal originated by the extracellular ligand
second messenger
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 …
sensory; rhodopsins
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
integral; N- and C- terminal segments
Many GPCRs are modified by n-glycosylation and/or by the palmitoylation of a cys residue, so they are also …
lipid-linked glycoproteins
by alternating between two discrete conformations, one with … bound and one without, the GPCR receptor can transmit an extracellular signal to the cell interior
agonist
…: G proteins that consist of an alpha, beta, and gamma subunit
heterotrimeric G proteins
the large alpha subunit of the heterotrimeric G protein consists of two domains connected by polypeptide linkers:
- a highly conserved … domain structurally similar to those in monomeric G proteins such as Ras, and is known as a … domain
- a … domain unique to them
GTPase; Ras-like; helical
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 …
beta propeller
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 …
GDP; GTP
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
switch regions
one of the major targets of the heterotrimeric G protein system is the enzyme …, which the binding of GTP to Galpha activates.
adenylate cyclase
…: stimulatory G protein
Gsalpha
inhibitory G proteins:
Gialpha
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
amplify
cells can adjust their … levels in response to a great variety of stimuli
cAMP
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
protein kinase A; cAMP-dependent protein kinase
the intracellular concentration of cAMP determines the fraction of PKA in its … form and thus the rate at which it .. its substrates
active; phosphorylates
the phosphoryl group at PKA’s Thr 197 functions to … its active site residues
properly orient
The R subunit of protein kinase A
competitively inhibits its C subunit
The R subunit contains two homologus cAMP-binding domains, Ra and Rb, and a so-called …, which blocks substrate binding
autoinhibitory segment
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
activation; inhibition
many drugs and toxins exert their effects by modifying components of the … system
adenylate cyclase
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
desensitization; changes in stimulation
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
beta-adrenergic receptor kinase; beta-arrestins
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 ..
amplitude; duration; subsequent signals
in the case of cAMP, this second messenger is hydrolyzed to AMP by enzymes known as …
cAMP-phosphodiesterases
The PDE superfamily, which includes both cAMP-PDEs and … is encoded in mammals by at least 20 different genes grouped into 12 families
cGMP-PDEs
PDEs may be activated by one/more of a variety of agents, including a calcium ion and phosphorylation by PKA and …
insulin-stimulated protein kinase
PDEs provide a means for crosstalk between … and those using other types of signals
cAMP-based signaling systems
