Lecture 14

Question 1

cell signalling

Answer 1

a signal transduction pathway is a series of steps by which a signal on a cells surface is converted into a specific cellular response

Question 2

Stages of cell signalling

Answer 2

reception
transduction
response

Question 3

discovery of the three stages of cell signalling

Answer 3

in 1971 an American biochemist won the Nobel prize for his discovery of how the hormone epinephrine acts on cells
Sutherland suggested that cells receiving signals went through the three processes

Question 4

Stage 1- reception

Answer 4

reception is the target cells detection of a signal molecule coming from outside the cell

the signal is detected when it binds to the membrane protein

Question 5

Reception process

Answer 5

a signal molecule binds to a receptor protein causing it to change shape

the binding between a single molecule (ligand) and receptor is highly specific

a shape change in a receptor is often the initial transduction of the signal

most signal receptor are plasma membrane protein

Question 6

Three main types of membrane proteins

Answer 6

G protein-coupled receptors
receptor tyrosine kinases
ion channel receptors

Question 7

G-coupled receptor

Answer 7

a plasma membrane receptor that works with the help of a G protein

the G protein acts as an on/off switch: if GDP is bound to the G protein, the G protein is inactive

Question 8

G-coupled receptor steps

Answer 8

1. when GDP is bound to the G protein its inactive
2. when the signalling molecule binds to the receptor it activates it and causes it to change shape. this change causes GDP to be released from the G protein and GTP to bind instead- activating the G protein
3. the activated G protein dissociated from the receptor, and binds to another enzyme causing a shape change and activation in that enzyme- this triggers a signal cascade
4. eventually the GTP is released from the G protein, GDP binds instead and the G protein returns to its inactive state

Question 9

Retinal and Rhodopsin

Answer 9

-11-cis and all trans retinal and the crystal structure of bovine rhodopsin

light causes the conversion 11-cis retinal to all trans retinal

this in turn causes a conformational change in rhodopsin

this leads to activation of its G protein on the intracellular side- as in all GPCRs

Question 10

G-protein linked receptors

Answer 10

contain 7 alpha helices spanning the membrane

coupled to a G-protein (acts as a switch)

Question 11

Receptor tyrosine kinases

Answer 11

can trigger more than one signal transduction pathway one amplifying signal

the receptor itself has enzymatic activity

intracellular part catalyses transfer of phosphates to tyrosine residues

Question 12

Ligand-gated channels

Answer 12

ligands acts as a gate to allow passage of ions through channels

Question 13

Receptor tyrosine kinases (RTKs) steps

Answer 13

1. during inactivity, the receptors exist as single units called monomers
2. when the signalling molecule binds to the extracellular part of the receptor it triggers dimerisation of the RTK
3. this causes activation of the intracellular part- the tyrosine kinase region- by adding phosphate groups to itself (activating it)
4. the activated regions the trigger activation of subsequent downstream enzymes, setting off a phosphorylation cascade and transduction of a signal cascade

Question 14

Ligand gated ions steps

Answer 14

1. in the absence of the ligand the gate is closed to the ions
2. when the ligand binds it causes shape change that opens up the gate to allow the ions through, the ions effect a cellular response
3. when the liand is released (or cleaved) from the receptor, it closes the gat so the ions can no longer pass through

Question 15

Protein phosphorylation and dephosphorylation

Answer 15

in many pathways, the signal is transmitted by a cascade of protein phosphorylation events

protein kinases add phosphates to a protein, this activates the protein

protein phosphatases remove phosphates from proteins, this deactivates the protein

this phosphorylation and dephosphorylation system acts as a molecular on/off switch

Question 16

A phosphorylation cascade

Answer 16

1. a series of different molecules in a pathway are phosphorylated inn turn, each molecule adding a phosphate group to the next one in line
2. active forms of each molecule have phosphates attached and are of a slightly different shape
3. the activation cascade continues until the signal reaches the nucleus (or another target) and causes the change in cellular activity

Question 17

Intracellular receptors

Answer 17

found in the cytoplasm or nucleus of target cells

small or hydrophobic chemical messengers can readily cross the membrane and active receptors

an activated hormone-receptor complex can act as a transcription factor, turning on or off specific genes

Question 18

Tranduction

Answer 18

the binding of the signalling molecule changes the receptor protein in some way, intimating the process of transaction

the transduction stage converts the signal to a form that can bring about a cellular response

Question 19

Multiple step signal transduction

Answer 19

the molecules involved are mostly proteins

multistep pathways can amplify a signal: a few molecules can produce a large cellular response

at each step the signals is transducer into a different form, usually a shape change in a protein

multistep pathways provide more opportunities for coordination and regulation the cellular response
–> not just relay but amplification of the signal and modulation of the response

Question 20

Response

Answer 20

the transducer signal brings about a cellular response: a change in cellular activity change in cytoskeleton or activation of genes in the nucleus

Question 21

Cell signalling and regulation of transcription or cytoplasmic activities

Answer 21

the cells response to an extracellular signal is sometimes called the output response

ultimately, a signal transaction pathway leads to regulation one or more cellular activities

the response may occur in the cytoplasm or may involve action in the nucleus

many signalling pathways regulate the synthesis of enzymes or other proteins usually by turning genes on or off in the nucleus

the final activated molecule in the cascade may function as a transcription factor

Question 22

Typical signalling pathway that leads to the regulation of gene activity in nucleus

Answer 22

1. the initial signalling molecules, the growth factor, triggers a phosphorylation cascade
2. once phosphorylated the last kinase in the sequence enters the nucleus and activated a transcription factor
3. this activated transcription factor molecule then stimulated transcription of a specific gene or genes
4. resulting in mRNA, then synthesis of a protein

Question 23

Two important benefits of multistep pathways

Answer 23

amplification of the signal
- at each step the number of activated products is much greater than in the preceding step
- because the active form of the protein is present long enough to activate more than one molecule at the next stage of the pathway, before they become inactive again

contribution the specificity of the response
- different kinds of cells have different collections of relay proteins
-these different proteins allow cells to detect and respond to different signals
- event the same signalling molecule can have different effects in cells with different proteins and pathways
-pathway branching and ‘cross-talk’ further helps the cell coordinate incoming signals

Question 24

Specificity of signalling

Answer 24

the particular type of proteins a cell possesses can determined what signalling molecule it responds to and the nature of the response

these 4 cells are all responding to the same signal molecule but in different ways

this is because the cells all contain different signalling proteins

some can inhibit other proteins and some can work together with other proteins to give a different response

Question 25

Second messengers

Answer 25

many signalling pathways involve 2nd messengers

these are small, non protein, water-soluble molecules or ions that spread throughout a cell by diffusion

2nd messengers participate in pathways initiated by GPCRs and RTKs

Cyclic AMP and calcium ions are common second messengers

Question 26

Cyclic AMP

Answer 26

cAMP is one of the most widely used 2nd messengers

adenylyl cyclase, an enzyme in the plasma membrane converts ATP to cAMP in response to an extracellular signal

Question 27

Calcium ions

Answer 27

are used widely as 2nd messengers

ca2+ can function as second messengers because its concentration in the cytosol is normally much lower than the concentration outside the cell

a small change in the number of calcium ions thus represents a relatively large change in calcium concentration

Question 28

Reversible cell damage

Answer 28

biochemical themes of reversible cell injury:
-ATP depletion
-Cellular swelling caused by changes in ion concentration
- changes in membrane permeability

Question 29

Necrosis and apoptosis

Answer 29

differ in their morphology, mechanism and roles in disease and physiology

Question 30

Apoptosis

Answer 30

programmed or controlled cell death

a cell is chopped and packaged into vesicles that are digested by scavenger cells

prevents enzymes from leaking out of a dying cell and damaging neighbouring cells

Question 31

Caspases

Answer 31

the main proteases that carry out apoptosis