Cell Signalling

Question 1

freception, transduction, response

outline ligand-receptor interaction

Answer 1

• receptor has a specific binding site with a 3D conformation that is complementary to that of the ligand
• binding of ligand to binding site of specific receptor forms ligand-receptor complex, causing receptor protein to undergo a change in 3D conformation
• chemical properties of ligands determine the location of receptors
• polar/hydrophilic hormones interact with receptors on cell surfac e membrane OR hydrophobic hormones interact with intracellular receptors
  *e.g. insulin binds to RTK OR glucagon binds to GPLR on the cell surface membrane

Question 2

outline signal transduction

Answer 2

• signal is transduced upon the change in 3D conformation of a receptor
• recruiting and activating the next immediate protein/enzyme (e.g. adenyl cyclase)
• result in the formation of the second messenger (cAMP)
• other downstream relay proteins/enzymes are activated by phosphorylation
• activation of enzymes in the signalling cascade leads to signal amplification
• steroid hormone receptor complex/activated relay protein acts as transcription factor to activate gene expression

Question 3

outline cellular response

Answer 3

• activation/inhibition of enzyme activities
• activation/inhibition of gene expression
• alteration in organelle functions
• alteration in membrane permeability to the transport of certain substances
• e.g. movement of GLUT to the cell surface membrane to increase uptake of glucose

Question 4

explain the nature of second messengers

Answer 4

• small and non-protein molecules or ions
• generated in large numbers in response to receptor activation
• large variety of proteins are sensitive to the concentrations of second messengers

Question 5

explain the roles of second messengers

Answer 5

• pass the signal from the signal molecule (first messenger) by binding to and altering the 3D conformation and behaviour of relay proteins or effector proteins, giving rise to a cellular response
• often diffuse away from their source, spreading the signal to other parts of the cell
• participate in pathways initiated by both GPLR and RTKs

Question 6

explain the role of cAMP

Answer 6

• component of many G-protein signalling pathways
• binding of signal molecule to receptor leads to activation of enzyme adenyl cyclase
• enzyme converts ATP to cAMP
• cAMP activates a protein kinase called protein kinase A, which activates other proteins via phosphorylation, giving rise to cellular responses
• phosphodiesterase converts cAMP to AMP
• if signal molecule is absent, rate of hydrolysis of cAMP is higher than rate of production of cAMP, decreasing cAMP production in the cell

Question 7

why are second messengers small?

Answer 7

• allows large amounts ot be stored in a cell
• allows them to diffuse throughout the cell quickly

Question 8

why are second messengers non-protein in nature?

Answer 8

• allows them to not be degraded by proteases/enzymes found in the cell
• allows them to not be affected by changing conditions in the cell (change in temp, pH) which proteins are sensitive to
• protein synthesis takes a longer time (unsuitable for rapid action) and takes up a lot of energy/resources

Question 9

explain the role of kinases in signal amplification

Answer 9

• protein kinases phosphorylate relay proteins (changing them from an inactive conformation into an active conformation)
• organised into phosphorylation cascades
• many relay molecules along a signal-transduction pathway are protein kinases and often act on one another

Question 10

explain the role of phosphatases in signal amplification

Answer 10

• enzymes that dephosphorylate relay proteins (changing them from the active conformation into an inactive conformation)
• effectively shut down signalling pathways when the extracellular signal is no longer present

Question 11

explain the role of relay proteins

Answer 11

• help relay the signal into the cell by generating second messengers or activating the next protein (relay or effector) in the pathway
• when relay proteins receive a signal, they switch from an inactive to an active conformation (through phosphorylation) until another process switches them off (dephosphorylation), returning them to their inactive conformation
• proteins can be phosphorylated by protein kinases
• protein phosphotases remove phosphate groups from proteins (dephosphorylate relay proteins), effectively shutting down signalling pathways when the extracellular signal is no longer present
• many of the relay molecules along a signal-transduction pathway are protein kinases and they often act on one another
• protein kinases often organised into phosphorylation cascades

Question 12

describe and explain signal amplification

Answer 12

• a signalling pathway with numerous steps between the initial signalling event at the cell surface and the cell’s response results in amplification of the signal and thus the response
• at each catalytic step in the signalling pathway, the number of activated products is much greater than in the preceding step, further amplifying the initial signal (cascade effect)
• amplification effect is due to the fact that these proteins persist in the active conformation long enough to process numerous molecules of substrate before they become inactive again
• one activated GPLR leads to the activation of several G proteins, each G protein activates a molecule of adenyl cyclase, each adenyl cyclase molecule catalyses the formation of many cAMP molecules, each cAMP activates a molecule of protein kinase A, each molecule of protein kinase A phosphorylates many molecules of the next kinase in the pathway, and so on
• as a result of the signal’s amplification, a small number of glucagon molecules binding to receptors on the surface of a liver cell can lead to the release of hundreds of millions of glucose molecules from glycogen

Question 13

outline how glucagon regulates the concentration of blood glucose concentration through G-protein linked receptor

Answer 13

• binding of glucagon to a GPLR causes the receptor to change 3D conformation, activating the receptor, which binds to and activates a specific G protein located on the cytoplasmic side of the plasma membrane
• G protein activation occurs when a GTP nucleotide replaces the GDP bound to the G protein
• activated G protein then acivates a membrane-bound enzyme adenyl cyclase
• activated adenyl cyclase converts ATP to cAMP, leading to an increase in concentration of cAMP
• cAMP acts as a second messenger and binds to and activates protein kinase A
• activated protein kinase A phosphorylates and activates glycogen phosphorylase, which catalyses the breakdown of glycogen to glucose
• activation of various enzymes in the cell (glycogen phosphorylase) results in the increase in blood glucose concentration through:
• glycogenolysis (liver cells): glycogen can be hydrolysed to glucose, which can be released back into the blood
• gluconeogenesis (liver cells): amino acids and triglycerides are converted to glucose in the liver
• inhibiting glycogenesis: inhibiting conversion of glucose to glycogen

Question 14

outline how insulin regulates the concentration of blood glucose concentration through receptor tyrosine kinase

Answer 14

• binding of insulin causes two receptor monomers to aggregate and form a dimer
• activates tyrosine kinase region of each polypeptide, which uses ATP to cross-phosphorylate the tyrosine residues on each other’s cytoplasmic tails
• different relay proteins now bind to specific phosphorylated tyrosines on the RTK and become phosphorylated due to the tyrosine kinase activity of the receptor. these relay proteins become activated, triggering many different transduction pathways in response to one type of signal
• activation of RTKs results in phosphorylation of several relay proteins, which lead to responses such as the translocation of the glucose transporter (GLUT4) to the cell surface membrane, increasing the uptake of glucose by cell
• blood glucose concentration can be reduced by:
• increased uptake of glucose into the cell (muscle and fat cells) by increasing permability of cell to glucosethrough translocation of glucose transporters to plasma membrane
• increased use of glucose as a respiratory substrate, therefore increasing the rate of respiration (muscle, fat and liver cells)
• increased glycogenesis (muscle and liver cells): glucose is converted to glycogen in the liver for storage
• increased lipogenesis (fat and liver cells): glucose is converted to fat for storage (activation of enzymes which synthesise lipids)
• increased uptake of amino acids
• increased rate of protein synthesis
• inhibit glycogenolysis and gluconeogenesis (muscle and liver cells)

Question 15

advantages of cell signalling pathways for multicellular organisms

Answer 15

• help cells respond to signal moleculed that are too large/too polar to cross CSM
• enable different cells to respond differently to the same signal as long as the cells carries the receptor on their CSM, such that the different cellular activities can be coordinated in response to a signal/many cells can be activated simulataneously
• help a target cell respond in different ways to just one signal as components of the signalling cascade may act on more than one pathway/numerous cellular responses can occur at once
• can amplify a signal through a cascade effect/a small number of signal molecules can result in a large number of activated molecules to bring about a response
• signal molecule at the CSM can activate genes in the nucleus without crossing the CSM