RTKs

Question 1

what are RTKs?

Answer 1

-a major class of transmembrane receptor found in multicellular organisms

Question 2

what are RTKs involved in?

Answer 2

• cell growth, movement and differentiation

- development and tissue repair

Question 3

what are the main ligands for RTKs?

Answer 3

growth factors: EGF, NGF, insulin

Question 4

what is the structure of RTKs?

Answer 4

extracellular domain that is  responsible for ligand binding. 
transmembrane helix (single a-helix of about 24 residues) 
intracellular domain with enzyme activity

Question 5

how does ligand binding cause a response in RTKs?

Answer 5

ligand -> conformational change -> receptor dimerises -> intracellular kinase domains can act on each other

Question 6

what is ligand induced oligomerisation?

Answer 6

the process by which RTKs dimerise in response to ligand

Question 7

how does RTK dimerisation affect kinase activity?

Answer 7

• triggers information transfer across the plasma membrane

- increases kinase activity

Question 8

why are RTKs inactive in the basal state?

Answer 8

substrate binding site is occluded by the regulatory domain, which has a hydroxyl group that prevents access to the kinase domain

Question 9

how is RTK activation dynamic?

Answer 9

the regulatory loop flips out, and will trigger autophosphorylation if threes a substrate molecule nearby

Question 10

what is the importance of the domains PTB and SH2 for RTK signalling?

Answer 10

mediate recruitment of signalling proteins

Question 11

which criteria determines SH2 domain specificity?

Answer 11

• the protein has to be tyrosine phosphorylated

- the residues nearby have to be specific to the SH2 domains they will bind to

Question 12

what are the advantages of RTKs recruiting multiple binding partners?

Answer 12

• localises signalling complexes to juxtamembrane regions
• increases efficiency of physical and functional interactions between proteins, permitting regulation of activity/phosphorylation