Unit 8.1 : Signal Transduction Pathways - I

Question 1

4 Steps: Gs-protein-coupled receptors that signal through the second messenger cAMP

Answer 1

(1) Ligand binding activates the receptor

(2) The heterotrimeric Gs protein associates with the receptor and is activated by the replacement of GDP for GTP.

(3) The a subunit dissociates from the by subunits and associates with adenylyl cyclase.

(4) Active adenylyl cyclase leads to the production of the second messenger cAMP (adenylyl cyclase converts ATP)

Question 2

Gs-protein-coupled receptors that signal through the second messenger cAMP:Turning the signal off requires (2):

Answer 2

(i) HYDROLYSIS of GTP on the a subunit to GDP and Pi

(ii) conversion of cAMP to AMP by a PHOSPHODIESTERASE ENZYME

Question 3

cAMP is formed from

Answer 3

ATP

**adenyl cyclase turns ATP into cAMP

Question 4

cAMP is formed from ATP by:

Answer 4

a CYCLIZATION REACTION that removes two phosphate groups from ATP and joins the “free” end of the remaining phosphate group to the sugar part of the ATP molecule.

Question 5

The conversion of cAMP to AMP is performed by a

Answer 5

phosphodiesterase enzyme

Question 6

The conversion of cAMP to AMP is performed by a phosphodiesterase enzyme that

Answer 6

reduces one of the ester bonds.

Question 7

The diverse effects of cAMP in animal cells are mediated by the action of

Answer 7

cAMP-dependent protein kinase (protein kinase A = PKA).

Question 8

The inactive form of PKA is a:

Answer 8

tetramer

Question 9

The inactive form of PKA is a tetramer, consisting of

Answer 9

two regulatory (R) and two catalytic (C) subunits.

Question 10

pka activation leads to:

Answer 10

the phosphorylation of downstream target proteins modulating their activity

Question 11

The inactive form of PKA is a tetramer, consisting of two regulatory (R) and two catalytic (C) subunits.
Each R subunit has:

Answer 11

two binding sites for cAMP
–> one pka can bind 4 camp

Question 12

Each R subunit has two binding sites for cAMP. Upon binding of cAMP to the regulatory subunits, the catalytic subunits

Answer 12

in their active form are released and can phosphorylate downstream target proteins.

Question 13

Adrenaline-mediated rise in cAMP is important in

Answer 13

mediating the body’s response to stress, such as fright or heavy exercise, when all tissues have an increased need for glucose and fatty acids.

Question 14

Adrenaline-mediated rise in cAMP is important in mediating the body’s response to stress, such as fright or heavy exercise, when all tissues have an increased need for glucose and fatty acids.
The responses are dictated by:

Answer 14

the types of receptors found in these cells and the types of signaling pathways that are activated.

Question 15

Adrenaline binds to

Answer 15

adrenergic receptors.

Question 16

b-adrenergic receptors are:

Answer 16

Gs receptors

Question 17

a-adrenergic receptors are

Answer 17

Gi receptors.

Question 18

adrenaline -> heart: major response

Answer 18

increase in heart rate and force of contraction (increased blood supply (nutrients) to tissues

Question 19

adrenaline -> skeletal muscle:major response:

Answer 19

glycogen breakdown

Question 20

adrenaline -> fat:major response:

Answer 20

fat breakdown

Question 21

Glycogen is a:

Answer 21

POLYMER of GLUCOSE and is the major storage form of this sugar.

Question 22

Glycogen Synthesis:

Answer 22

Glucose is coupled to UDP and then incorporated into the glycogen polymer by GLYCOGEN SYNTHASE.

Question 23

Glycogen Breakdown:

Answer 23

GLYCOGEN PHOSPHORYLASE
removes glucose as glucose-1-phosphate when glucose is needed.

Question 24

What are the two enzymes involved in glycogen synthesis and breakdown

Answer 24

Synthesis: Glycogen Synthase
Breakdown: Glycogen Phosphorylase

Question 25

Glycogen metabolism: tissue specific regulation: what happens to glucose 1 phosphate in muscles vs in liver:

Answer 25

in muscles: glucose 1 phosphate is converted to glucose 6 phosphate in liver: phosphate is removed from glucose-1-phosphate and glucose absorbed in blood

Question 26

Adenylyl cyclase

Answer 26

an enzyme that converts ATP to cyclic AMP

Question 27

Glycogen metabolism: One target of PKA is glycogen synthase. The phosphorylated form is;

Answer 27

inactive and this prevents glycogen production. It can be restored to its active form by the actions of a phosphatase called protein phosphatase 1.

Question 28

phosphorylated form of glycogen synthase is:

Answer 28

inactive (and this prevents glycogen production)

Question 29

phosphorylated glycogen synthase is inactive: it can be restored to its active form by:

Answer 29

the actions of a phosphatase called protein phosphatase 1

Question 30

Another target of PKA is phosphorylase kinase. Once this kinase is phosphorylated, it is

Answer 30

activated. This activation is also reversible by protein phosphatase 1.

Question 31

PHOSPHORYLATED phosphorylase kinase is :

Answer 31

active

Question 32

phorylated phosphorylase kinase is active, and can be reversed by:

Answer 32

phosphatase 1

Question 33

The pka has two types of pathways:

Answer 33

(1) fast (second - minutes) (2) slow (minutes to hours)

Question 34

The PKA pathway has fast and slow responses: fast responses involve:

Answer 34

Signal transduction in the cytosol involving activation of PKA, phosphorylation of glycogen synthase, phosphorylase kinase and glycogen phosphorylase.

Question 35

The PKA pathway has fast and slow responses: slow response (minute to hours) include:

Answer 35

cAMP-inducible gene transcription

Question 36

cAMP- inducible gene transcription: The PKA pathway can regulate gene expression by:

Answer 36

activating transcription factors that bind to cAMP response elements (CREB) in the DNA.

Question 37

cAMP- inducible gene transcription:All cAMP-responsive genes have a

Answer 37

DNA sequence upstream of the gene called a cAMP response element (CRE).

Question 38

cAMP- inducible gene transcription:What happens after CREB gets activated?

Answer 38

CREB then dimerizes and binds to the CRE sequence. This then recruits a protein complex composed of CBP and p300 and other proteins that modify the DNA such that it becomes transriptionally active.

Question 39

pka pathway slow response (3 steps):

Answer 39

1. free catalytic subunit of protein kinase A translocates to the nucleaus through nuclear pores 2.it phosphorylates and activates a transcription factor called CREB 3. CREB dimerizes and binds to CRE sequence, this the recruits a protein complex and other proteins that modify DNA such that it becomes transcriptionally active

Question 40

CREB

Answer 40

cAMP response element binding proteins

Question 41

All cAMP-responsive genes have a

Answer 41

DNA sequence upstream of the gene called a cAMP response element (CRE).

Question 42

cAMP-Inducible Gene Transcription

Answer 42

PKA Translocation: The free catalytic subunit of PKA translocates to the nucleus. CREB Activation: PKA phosphorylates and activates CREB (cAMP response element-binding protein). CRE Sequences: cAMP-responsive genes have a CRE sequence upstream of the gene. Transcriptional Activation: CREB dimerizes and binds to the CRE sequence. This recruits a protein complex composed of CBP and p300, which modify the DNA to make it transcriptionally active.

Question 43

Turning off the adrenaline/glucagon signal (4):

Answer 43

1. Affinity between receptor and ligand decreases in the presence of activated Gsa, limiting the number of Gsa proteins that are activated.à 2. Hydrolysis of GTP on Gsa is increased by adenylyl cyclase (like a GAP protein) 3. Phosphodiesterase converts cAMP to AMP, lessening the signal. 4. The b-adrenergic receptor itself becomes a substrate for both PKA and another kinase called BARK (b-adrenergic receptor kinase) that desensitize it.

Question 44

Some second messengers are derived from phosphatidylinositol. The inositol group can be phosphorylated by several kinases at either

Answer 44

the 4 or 5 position of the ring

Question 45

A phospholipase C enzyme can then hydrolyze the inositol ring releasing two second messengers

Answer 45

diacylglycerol (DAG) and inositol-1,4,5- triphosphate (IP3).

Question 46

A phospholipase C enzyme can then hydrolyze the inositol ring releasing two second messengers: diacylglycerol (DAG) and inositol-1,4,5- triphosphate (IP3).The second messengers DAG and IP3 then trigger separate downstream events ;

Answer 46

(1) DAG remains membrane associated (2) IP3 is hydrophilic and can diffuse in the cytosol

Question 47

G-protein coupled receptors also signal through phospholipids and Ca2+ Two phospholipase C (PLC) isoforms:

Answer 47

1. PLC-b – Activated through Gq-associated receptors via the Gqa subunit. Vasopressin, acetylcholine and thrombin signal through such receptors. 2. PLC-g – activated through receptor tyrosine kinases (RTKs)

Question 48

Gq vs Gs or Gi?

Answer 48

Gq is a type of G-protein alpha subunit that activates a different signaling pathway than Gs or Gi. Instead of regulating adenylate cyclase and cAMP, Gq activates phospholipase C (PLC), which triggers the IP₃/DAG pathway.

Question 49

__ is a protein that binds to calcium ions

Answer 49

calmodulin

Question 50

In the calcium bound state: calmodulin binds to:

Answer 50

other CaM kinases and other proteins to elicit diverse responses

Question 51

once calmodulin binds CaM kinases and other proteins it elicits diverse responses such as:

Answer 51

(1) Phoshorylates the myosin light chain (2) activation of PDE 1 reducing levels in cytosol (3) Phosphorylation and activation of CREB protein: transcriptipn of various genes

Question 52

Describe the 3 steps involved: Regulation of Muscle Contraction by Ca 2+ and CaM:

Answer 52

(1) A rise in intracellular Ca2+ causes Ca2+ to bind to CaM (2) CaMCa2+ activates myosin light chain kinase (MLCK) (a CaM kinase) (3) MLCK phosphorylates the light chain of myosin which then binds to actin to initiate muscle contraction

Question 53

Regulation of CREB Transcriptional activity by Ca2+ and CaM (4):

Answer 53

(1) A rise in intracellular Ca2+ causes Ca2+ to bind to CaM (2) CaM Ca2+ activates CaMKII ( a CaM kinase) (3) CamKII enters the nucleus through the pores and phosphorylates CREB (4) CREB dimerizes and binds to DNA at CRE sequences, and recruits p3000 and CBP to activate gene transcription

Question 54

Regulation of cAMP levels by Ca2+ and CaM (3):

Answer 54

(1) A rise in intracellular Ca2+ causes Ca2+ to bind to CaM (2) CaM Ca2+ activates calcium-calmodulin dependant phosphodiesterase 1 (PDE1), highly expressed in brain, heart, lung. (3) PDE1 converts cAMP (produced by adenyl cyclase) to AMP, downregulating cAMP=dependant signaling pathways

Question 55

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