Receptor Mechanism III

Question 1

Name 4 examples of enzyme linked receptors

Answer 1

Tyrosine receptors kinase
JAK/STAT
Serine threonine receptor kinase

Question 2

Name 3 features of enzyme-linked receptors

Answer 2

Predominantly single transmembrane domain receptors

Activation leads to activation of receptor kinases

Activation leads to the activation of multiple signalling pathways

Question 3

What processes are enzyme-linked receptors involved in

Answer 3

Cell growth
Division
Differentiation
Survival
Migration

Question 4

What happens when an agonist binds to a kinase receptor

Answer 4

Dimerisation of agonist and phosphorylation of specific residues (e.g. tyrosine)

Question 5

What does Grb-2 bind to and what happens

Answer 5

Tyrosine through SH2 domains, then interacts and binds with GEF (guanine-nucleotide exchange factor) through SH3 domains.

GEF activates RAS with GDP.

Question 6

What happens when RAS is activated

Answer 6

GDP is expelled and exchanged for GTP, to form Ras-GTP -> more intracellular pathways.

Question 7

describe activation of PI 3-kinase

Answer 7

Phosphorylates PIP2 to PIP3 -> Binds to PDK1 and PKB

PDK1 phosphorylates PKB and activates PKB so it dissociates

Question 8

Describe insulin receptor vs tyrosine kinase receptor

Answer 8

Alpha chain
Disulphide links
Beta chain

Question 9

Describe insulin receptor action

Answer 9

Conformational change, beta subunits brought together for phosphorylation, recruiting IRS through SH2 domain.

Question 10

What does IRS do

Answer 10

IRS recruits activated PI 3-kinase, (and Ras, phospholipase C) phosphorylated to PIP3 then PDK1 then PKB, dissociation to active PKB. Glycogen synthesis, protein synthesis

Question 11

What do kinases do vs what do phosphatases do

Answer 11

Kinases add phosphates

Phosphatases remove phosphates

Question 12

Describe the activation of phosphatases

Answer 12

Activation of receptors leads to phosphorylation, de-phosphorylation leads to inactivation

Phosphatases are activated.

The signalling procvess sets in motion events that lead to signal termination

Question 13

Inactivation of Ras

Answer 13

GDP replaced by GTP to form active complex with Raf.

Question 14

What does active Ras do

Answer 14

Interacts with GTPase activating protein (GAP), stimulating GTPase activation.

GTP dissociates, Ras deactivated to inactive form.

Question 15

Describe some harmful mutations in key regulatory mechanisms

Answer 15

Loss of phosphatase activity - Increased phosphates
Receptor expression - Increases
Loss of GTPase activity - Increased Ras activity
Loss of phosphatases - Inhibiting inactivation proces

Question 16

Describe some harmful mutations in key regulatory mechanisms

Answer 16

Loss of phosphatase activity - Increased phosphates
Receptor expression - Increases
Loss of GTPase activity - Increased Ras activity
Loss of phosphatases - Inhibiting inactivation process

Question 17

What happens when a ligand growth hormone binds to a JAK-stat receptor

Answer 17

Dimerisation, phosphorylation of JAK proteins. Receptor itself is phosphorylated. Receptor acts as docking site for STAT. Dimer formed.

Dimer dissociates and migrates to nucleus, stimulating/regulating gene expression at target gene.

Question 18

Describe serine-threonine kinase receptor. (E.g. TGF-Beta)

Answer 18

Requires type 1 and type 2 receptors, where both have serine/threonine kinase domain.

TGF-beta molecule binds to type II receptor, leading to conformational change, dimerisation with type 1 receptor.

Type 2 receptor phosphorylates type 1 receptor, leading to recruitment of Smad2 and Smad3. Phosphorylation of Smad.

Smad dimerises with Smad4, and dissociates. The dimer moves to the nucleus, where it regulates gene expression.

Question 19

What are intracellular receptors activated by

Answer 19

Molecules that readily pass across the plasma membrane, and are largely insoluble in aqueous environments e.g. thyroid hormones.

Question 20

Describe steroid receptor mechanism (e.g. cortisol)

Answer 20

Cytosolic receptor - Bound to heatshock protein (HSP). Cortisol binds to HSP+GR protein (glucocorticoid receptor) causing dissociation of HSP. GR with glucocorticoid forms dimer.

Dimer moves into nucleus where it binds to a glucocorticoid response element, leading to transcription increase.

Question 21

Describe thyroid hormone receptor mechanism

Answer 21

T3 (Thyroid hormone) bound to binding globulin, diffuses into nucleus. Binds to thyroid hormone receptor. Activates other associated proteins to form thyroid response element, to lead to transcription.