Signal Transduction

Question 1

Kd =?

Answer 1

(R)(L)/ (RL)

Question 2

What is signal integration? give an example

Answer 2

multiple different pathways that “converge on the same node” (i.e. two pathways that
result in the same response

calcium released in the muscle as an example:
calcium causes the release of glucose to be used for ATP production, which will fuel
muscle contraction. Additionally, calcium interacts with the proteins in muscle to allow
for the physical contraction to take place.

Question 3

What is generation of Calcium

Answer 3

released into cytoplasm from endoplasmic reticulum (ER) or extracellular
space

Question 4

what are effects of calcium - a second messenger

Answer 4

activates both protein kinase C (PKC) and calmodulin (note: calmodulin binds
to and activates proteins ).

Question 5

generation of Cyclic nucleotides (cAMP, cGMP):

Answer 5

: adenylyl and guanylyl cyclase convert ATP and GTP into cAMP and cGMP
(respectively) via attachment of the 5’ and 3’ carbons through a phosphodiester bond.

Question 6

effects of second messenger Cyclic nucleotides (cAMP, cGMP):

Answer 6

cAMP activates Protein Kinase A (PKA) ; cGMP activates protein kinase G
(PKG)

Question 7

generation of Inositol trisphosphate (IP 3) and diacylglycerol (DAG)

Answer 7

activated phospholipase C cleaves
membrane-bound phosphatidylinositol-4,5-bisphosphate
(PIP 2) (please note the cleavage site! Dr. Jones
emphasizes its importance a couple of times in lecture

Question 8

effects of Inositol trisphosphate (IP 3) and diacylglycerol (DAG)

Answer 8

diffuse away from the membrane into the
cytoplasm and transduce its signal, while DAG remains
membrane-bound and can activate other proteins in the
lipid bilayer

Question 9

Is small GTP binding proteins like ras second messengers?

Answer 9

no
Ras is GDP-bound. It is activated by guanine exchange
factor (GEF) , which “kicks” the GDP off. Because intracellular [GTP] is ~10x greater
than [GDP], GTP binds the protein.

Question 10

what are the three subunits of Heterotrimeric G proteins their targets and effects

Answer 10

i. G s s timulates adenylyl cyclase
ii. G i i nhibits adenylyl cyclase
iii. G q
(“q” for the quirky one) activates PLC

Question 11

What are two examples of G protein coupled receptors?

Answer 11

cAMP and IP3 and DAG

Question 12

which receptor interacts with heterotrimeric G protein on the cytoplasmic side of the membrane.

Answer 12

G protein coupled receptors

Question 13

what is cAMP

Answer 13

the G salpha subunit dissociates when the receptor binds its ligand to activate
adenylyl cyclase, and the resulting cAMP activates PKA (e.g. beta-adrenergic
receptor

Question 14

what activates IP3 and DAG

Answer 14

PLC then IP 3 activates a channel on the ER which increases
[Ca 2+ ] in the cell, activating calmodulin (which will also activate other proteins!) and
PKC.

Question 15

what are receptor tyrosine kinases (RTKs)

Answer 15

membrane-spanning receptors dimerize upon ligand binding,
and they undergo activation by auto-phosphorylation on
tyrosine residues

Question 16

what is bound by associated adaptor molecules ,
which set off a signaling cascade.

Answer 16

phosphotyrosines

Question 17

whats an example of receptor tyrosine kinase?

Answer 17

insulin receptor

Question 18

describe Receptor Guanulyl cyclases?

Answer 18

, these receptors will dimerize upon
ligand binding, activating guanylyl cyclase on the cytoplasmic membrane. The resultant cGMP
goes on to activate PKG , initiating downstream effects. These receptors are primarily involved
in body fluid level maintenance . Another variant of this receptor resides wholly in the
cytoplasm , and this is the nitrous oxide (NO) receptor. It is capable of remaining in the
cytoplasm because NO can diffuse across the membrane , therefore no extracellular receptor is
needed.

Question 19

what are adhesion receptors (integrins)

Answer 19

these receptors span the membrane, but they are unique
because they exhibit outside-in signaling (contact with ECM) and inside-out signaling
(interaction on the cytoplasmic membrane with the talin protein).

Question 20

what are the three different conformations of integrins

Answer 20

a. Low affinity : neither type of signaling present
b. Intermediate affinity : only one type of signaling present
c. High affinity : both types of signaling present

Question 21

which receptor do platelets make use of its high affinity conformation? in order to form clots

Answer 21

adhesion receptors integrins

Question 22

what are notch receptors

Answer 22

: the ligand for this receptor is a cell surface protein from another cell (known
as the instructing cell )

Question 23

what receptors are crucial for mediating cell - cell interactions

Answer 23

notch receptors

Question 24

true or false
notch receptor undergoes
intramembrane cleavage, and the cytosolic portion of the receptor diffuses away from the
membrane and travels to the nucleus to act as a transcription factor .

Answer 24

True

Question 25

what are nuclear receptors

Answer 25

these are crucial for the signaling mediated by fat-soluble hormones (i.e.
can diffuse through the cell membrane).

Question 26

what are two types of nuclear receptors

Answer 26

Type I receptors live in
the cytoplasm and they travel to the nucleus where they influence transcription. Type II receptors live in the nucleus , and sometimes on the target DNA itself, where they also influence
transcription.

Question 27

true or false a single ligand-receptor interaction can cause a relatively large response

Answer 27

true

Question 28

What are the reactions catalyzed by both adenylyl cyclase and PLC? (answer at the end of
the noteset)

Answer 28

adenylyl cyclase converts ATP into cAMP . PLC cleaves PIP 2
, forming IP 3
(diffuses freely through the cytoplasm) and DAG (remains membrane-bound).