Mol Lecture #37

Question 1

Receptor tyrosine kinases (RTKs)

overview

Answer 1

• Family of cell surface receptors that have a kinase on their cytoplasmic portion
• 58 types in humans
• Protein ligands
  –> Regulate many processes
• Extracellular signalling molecule binds to a receptor to produce a conformational change

Question 2

Reception

Answer 2

• Ligand binding produces dimerization in a conformational change (activation of an enzyme)
• The green protein only binds when the phosphate is added (autophosphorylation )to tyrosine (changes the binding affinity)
  –>Recruitment of proteins changes the activation of signalling pathways

Question 3

Transduction

Answer 3

• When Inactive Ras (GTPase) is activated it activates a series of kinases
• Changing activity through kinases
• Changing amount of transcription through transcription factors binding to elements

Question 4

GTPase (Ras)

Picture also in camera roll

Answer 4

• A protein that can bind and hydrolyze GTP conformational change(GTP → (get a phosphate from it) GDP) same way as ATP hydrolysis
• Serves as a molecular switch to control signalling events
• Two types: Small monomeric GTPases and trimeric GTPases
• Ras is a monomeric GTPase

Question 5

Kinase Cascade

Answer 5

• Series of kinases called MAPks that help to amplify the signal
• Kinases (an enzyme) can phosphorylate other proteins
  –> Can also activate transcription factors
• Each one acts more than the previous stage

Question 6

Response

Answer 6

• Responses are unique to the ligand/receptor pair AND to the cellular conext in which they are happening

Question 7

Insulin Receptor

Response Example

Answer 7

• Insulin is a protein (RTKs really respond to proteins) hormone (long distances) that is released by the beta cells in the pancreas to help reduce blood glucose concentration.
• Endocrine
  –> Mutations in the receptor can lead to diabetes
• Insulin binds RTK → Ras → kinase (MAPK) → responses

Question 8

Insulin Receptor

Liver

Answer 8

In the liver:
1) Glut4 is brought to the surface to increase glucose transport into the cell
2) Stimulates glucose storage in the form of glycogen by dephosphorylating glycogen synthase.
3) Increase glycoylsis by increasing transcription of phosphofructokinase (critical thing for glycolysis) →
4) Insulin promotes the synthesis of fatty acids in the liver from acetyl-CoA by dephosphorylating Acetyl-CoA carboxylase. (for the storage of glucose)

Question 9

G-protein-coupled receptors (GPCR)

Overview

Answer 9

• 7 transmembrane domains
• Approximately 800 in humans
• Receptor activates an associated GTPases and causes the generation of small molecule ‘second messengers’ which then activates kinases

Question 10

G-protein coupled receptos (GPCR)

Answer 10

• Use trimeric GTPases
• Addition of GTP causes signalling
• When binding to ligand there is going to be conformational change
• Second messengers are small molecule intermediates used in signalling (sm’s cause the downstream activation of kinase)

Question 11

cAMP receptor-response pathways (GPCR)

Answer 11

• Cyclic is the second messenger that activates downstream kinase called PKA
• Ligand/GPCR → GTPase→ adenyl cyclase → cAMP → protein kinase A
• Phosphodieserase can make cAMP inactive by converting it directly to AMP