Test 3. Lecture 32

Question 1

_________________are the largest family of cell surface receptors.
Signals are transmitted via guanine nucleotide-binding proteins (G proteins).
The receptors have seven membrane-spanning α helices.

Answer 1

G protein-coupled receptors

G proteins

Question 2

Binding of a ligand induces a conformational change that allows the cytosolic domain to
activate a G protein on the inner face of the plasma membrane.

The activated G protein then dissociates from the receptor and carries the signal to an
intracellular target.

G proteins were discovered during studies of cyclic AMP (cAMP), a second messenger
that mediates responses to many hormones.

A G protein is an intermediary in ___________activation, which synthesizes ______________.

Answer 2

adenylyl cyclase

cAMP

Question 3

G proteins have three subunits designated α, β, and γ.

They are called _______________

The α subunit binds guanine nucleotides, which ___________

In the inactive state, α is bound to GDP in a complex with β and γ.

Answer 3

α, β, and γ.

heterotrimeric G proteins.

regulate G protein activity.

Question 4

Hormone binding to the receptor causes exchange of GTP for GDP.
The _____________________ from the receptor and interact
with their targets.

α SUBUNIT STIMULATES ADENYLYL CYCLASE, WHICH CATALYZES THE CONVERSION OF ATP TO cAMP

Answer 4

α and βγ complex then dissociate

Question 5

1. ____________:
   Chain of reactions that transmits signals from the cell surface to
   intracellular targets.
2. Targets often include transcription factors that regulate gene
   expression.
3. Intracellular signaling was first studied in hormones like epinephrine,
   which signals the breakdown of glycogen to glucose.
4. In 1958 Sutherland discovered that epinephrine action was mediated
   by an increase in ___________-, leading to the concept of
   cAMP as a_____________.

Answer 5

Intracellular signal transduction

cyclic AMP (cAMP) 
second messenger

Question 6

cAMP effects are mediated by ______________________, or
_____________

Inactive form has two regulatory and two
catalytic subunits. cAMP binds to the regulatory subunits, which dissociate the kinase.

The free catalytic subunits can then phosphorylate serine on target
proteins.

Answer 6

cAMPdependent protein kinase

protein kinase A.

Question 7

” regulation of glycogen metabolism by epinephrine”

The epinephrine receptor is coupled to adenylyl cyclase via a __________ that
stimulates enzymatic activity, increasing the concentration of cAMP.

Answer 7

G protein

Question 8

In glycogen metabolism, protein kinase A

phosphorylates what two enzymes?:

Answer 8

• Phosphorylase kinase is activated, and in turn activates glycogen
phosphorylase, which catalyzes
glycogen breakdown.

• Glycogen synthase is inactivated, so glycogen synthesis is blocked.

Question 9

In many animal cells, increases in cAMP activate transcription of genes
that have a regulatory sequence called ____________

The free catalytic subunit of protein kinase A goes to the nucleus and
phosphorylates transcription factor ____________

Answer 9

cAMP response element
(CRE).

CREB (CRE-binding protein).

Question 10

Phosphorylation of CREB
leads to recruitment of
coactivators and
expression of cAMPinducible
genes.

Regulation of gene
expression by cAMP plays
important roles in many
aspects of ______________

Answer 10

cell behavior

Question 11

Protein kinases don’t function in__________.

Protein phosphorylation is rapidly reversed by protein
phosphatases, which terminate responses initiated by receptor activation of protein kinases

Answer 11

isolation

Question 12

How can cAMP regulate ion channels?

Answer 12

It is a second messenger in sensing smells—odorant receptors are
G protein-coupled. They stimulate adenylyl cyclase, leading to
increased cAMP.

cAMP opens Na+ channels in the plasma membrane, leading to
initiation of a nerve impulse.

Question 13

_____________ is another important second messenger.
cGMP is formed from GTP by guanylyl cyclases and degraded to GMP by a phosphodiesterase.

cGMP mediates biological responses, such as blood vessel
dilation.

Answer 13

Cyclic GMP (cGMP)

Question 14

In the vertebrate eye, __________ is the second messenger that converts visual signals
to nerve impulses

Answer 14

cGMP

Question 15

The photoreceptor in retinal rod cells is a G protein-coupled receptor called
_____________.

 Rhodopsin is activated when light is absorbed by the associated molecule 11-
cis-retinal, which isomerizes to all-trans-retinal.

 Rhodopsin then activates the G protein __________.

 Transducin stimulates _________________-, leading to decreased levels
of cGMP.

 cGMP levels are translated to nerve impulses by a direct effect of cGMP on ion
channels.

Answer 15

rhodopsin

transducin

cGMP phosphodiesterase

Question 16

Other cell surface receptors are directly linked to intracellular enzymes.
The largest family of these are the___________, which phosphorylate their substrates on tyrosine residues.

Answer 16

tyrosine kinases

Question 17

Receptor tyrosine kinases

Includes the receptors for ________________

Answer 17

most polypeptide growth factors.

Question 18

The human genome encodes 58 receptor tyrosine kinases, including the receptors for __________________________

Answer 18

EGF, NGF, PDGF, insulin, and many other growth

factors.

Question 19

all receptor tyrosine kinases have:

Answer 19

• An N-terminal extracellular ligand-binding domain
• One transmembrane α helix
• A cytosolic C-terminal domain with protein-tyrosine kinase activity

Question 20

Binding of ligands (___________) to the extracellular domains activates their
cytosolic kinase domains.

This results in ___________ the receptors and intracellular target
proteins that propagate the signal.

• The first step is LIGAND=INDUCED RECEPTOR DIMERIZATION

• This results in receptor ____________________-, as the two polypeptide chains
cross-phosphorylate each other

Answer 20

growth factors
phosphorylation of both

autophosphorylation

Question 21

what are the two roles of autophosphorlation?

Answer 21

Phosphorylation of tyrosine in the catalytic domain increases protein kinase activity.

• Phosphorylation of tyrosine outside the catalytic domain creates binding sites for
other proteins that transmit signals downstream from the activated receptors.
Downstream signaling molecules have domains, such as SH2, that bind to specific phosphotyrosine-containing peptides of the activated receptors.

Question 22

\_\_\_\_\_\_\_\_\_\_\_\_\_\_ were the
first to be characterized,
initially recognized in
protein-tyrosine kinases
related to Src, the
oncogenic protein of Rous
sarcoma virus.

Answer 22

SH2 domains