Block D

Question 1

what are the surface receptors

Answer 1

enzyme-linked receptors (recognise various type pf signalling molecule)
G-protein coupled receptors (GPCR)
Ligand-gated ion channel

Question 2

Epidermal growth factor

Answer 2

Stimulates cell growth and division

Question 3

EGF signal transduction pathway

Answer 3

1. receptor activates 2 EGF molecule and binds to 2 EGF receptor subunit causing them to dimense and phosphorlate each other on tyrosine.

2. Relay between the receptor
and protein kinase cascade:
Grb binds to the phosphorylated
receptor and then to Sos. Sos
stimulates Ras to release GDP
and bind GTP.

3.Protein kinase cascade:
Ras activates Raf, which starts a
protein kinase cascade in which Raf
phosphorylates Mek, and then Mek
phosphorylates Erk.

4. Activation of
transcription factors:
Erk enters the nucleus
and phosphorylates
transcription factors,
Myc and Fos.

5. Cellular response: Myc and Fos
stimulate the transcription
of specific genes. The mRNAs
are translated into proteins that
cause the cell to progress
through the cell cycle and divide

Question 4

G- protein-coupled receptor

Answer 4

> signal that bind to cell surface receptors are the first messenger.
Binding of signals to GPCRs often lead to the production of intracellular second messengers.

Question 5

Second messengers

Answer 5

cAMP
Ca2+
Diacylglycerol (DAG)
inositol
triphosphate(IP3)

Question 6

cAMP

Answer 6

cyclic adenosine monophosphate

Question 7

Signal transduction via cAMP

Answer 7

Activation of GPCR by signalling molecule stimulates GTP binding by Ga subunit releasing it from Gbetay

alpha subunit binds to and activates adenylyl cyclase enzyme, stimulating cAMP synthesis

Question 8

cAMP activates protein kinas A (PKA)

Answer 8

Binding of cAMP to protein kinase A (PKA) activates the kinase enzyme activity
Activated PKA phosphorylates specific intracellular proteins, including enzymes, structural proteins and transcription factors…resulting in a cellular response

Question 9

Adrenaline (epinesphrine) binds to a GPCR leading to production of cAMP

Answer 9

1. The binding of
epinephrine
activates a GPCR.
This causes the G
protein to bind GTP,
thereby promoting
the dissociation of
the a subunit from
the β/Y dimer.

2.The binding of the α subunit to adenylyl cyclase promotes
the synthesis of cAMP from ATP.

3.cAMP binds to the regulatory subunits of PKA, which releases the catalytic subunits of PKA

4. The catalytic subunits of PKA use ATP to phosphorylate specific cellular proteins and thereby cause a cellular
   response.

Question 10

PKA phosphorylates enzymes involved in glycogen breakdown and synthesus

Answer 10

Adrenaline mediates the “fight or flight response”…the ability to respond to a stressful situation
Activation of PKA in skeletal muscle leads to the breakdown of muscle glycogen to glucose-6-phosphate, which is used to supply the muscles with ATP (energy)
This effect of PKA is via the phosphorylation of key enzymes involved in glycogen breakdown and synthe

Question 11

Reversal of the cellular response to adrenaline

Answer 11

signaling involving second messengers is generally of short duration.
as the level of signaling molecule decreases the number of activated receptors decreases.
Inside the cell, the a subunit hydrolyses its GTP to GDP and re-associates with b/y to form an inactive G protein.
Levels of cAMP fall as adenylyl cyclase is no longer being activated and an enzyme known as a phosphodiesterase converts cAMP to AMP
Reduced levels of cAMP lead to an inhibition of PKA
Protein phosphatases remove phosphate groups from proteins, reversing effects of PKA

Question 12

advantages of second messengers are signal amplification and speed.

Answer 12

signal amplification- binding of signal to a receptor produce many cAMP molecules that activate PKA which phosphorylate many protein.
Speed- large amount of cAMP can be produced very rapidly and can diffuse quickly through the cell

Question 13

second messengers

Answer 13

IP3 and DAG are second messengers which activates g-protein and signal transduction.
alpha subunit activates the enzyme phospholipase C.
Phospholipase C cleaves the plasma membrane phospholipid PIP2, producing diacylglycerol (DAG) and inositol triphosphate (IP3)
IP3 opens Ca2+ channels in endoplasmic reticulum, increasing levels of cytosolic Ca2+
DAG activates protein kinase C (PKC)

Question 14

signal transduction pathway involving DAG, IP3 and Ca2+

Answer 14

1. A signaling molecule
   activates a GPCR, thereby activating the α subunit of the G protein
   2.The α subunit of this G protein binds to phospholipase C, causing it to cleave a bond in a membrane phospholipid,
   and producing DAG and IP3.
   3.Binding of IP3 to Ca2+
   channels in the ER causes them to open and release many Ca2+ into the cytosol.
   4.Binding of DAG and Ca2+
   to PKC activates PKC, which then phosphorylates proteins and leads to a cellular response.
   5.Binding of Ca2+ to calmodulin activates its function, which regulates proteins and also leads to a cellular response.