Kinase Linked receptors

Question 1

Name the 5 main types of enzyme-linked receptors

Answer 1

RTKs
Receptor Serine/Threonine kinase
Tyrosine Kinase-associated receptors
Receptor Guanylyl Cyclases
Receptor Tyrosine Phosphatases

Question 2

What do RTKs transduce signals to ?

Answer 2

polypeptide + protein hormones

growth factors

Question 3

Describe how RTKs are activated

Answer 3

• ligand binds to receptor
• conformational change
• tyrosine kinase is phosphorylated
• the signalling proteins activate the receptor

Question 4

Name a type of RTK

Answer 4

EGFR (epidermal growth factor receptor)

Question 5

What does drysregulation of EF/EGFR expression lead to?

Answer 5

cancer development

Question 6

What does EGF/EGFR signalling promote?

Answer 6

• embryonic development
• stem cell regeneration
• regulation of ion transport
• wound healing

Question 7

Describe the typical structure of an RTK e.g. EGFR

Answer 7

• extracellular LBD
• TM helix domain
• intracellular catalytic/tyrosine kinase domain
• juxtamembrane + adaptor domains with tyrosine residues

Question 8

Define dimerization

Answer 8

combination of two identical molecules to form a dimer

Question 9

Binding of EGR causes the ______ of EGFR monomers leading to a ______ change. This triggers trans + auto-___________ of tyrosine residues, which initiate signalling cascades

Answer 9

dimerization
conformational
phosphorylation

Question 10

What are the 2 main downstream signalling pathways triggered by activated EGFRs?

Answer 10

• RAS/MAPK

- PI3K/AKT

Question 11

What are RTKs key regulators of?

Answer 11

• proliferation
• differentiation
• cell survival + metabolism
• cell migration
• cell cycle control

Question 12

Tyrosine Kinase-associated receptors transduce signals to _____

Answer 12

cytokines

Question 13

What cells produce cytokines?

Answer 13

immune cells

Question 14

What are the functions of cytokines?

Answer 14

• cell communication
• cell development
• differentiation
• immune + inflammatory response

Question 15

Name a cytokine receptor signalling pathway

Answer 15

JAK/STAT

Question 16

What are JAKs?

Answer 16

family of non-receptor tyrosine protein kinases that convert stimuli into cellular processes

Question 17

What are STATs?

Answer 17

A family of transcription factors + SH2 domain proteins

Question 18

Oncogenic transformation may result from loss of auto-control mechanisms via what

Answer 18

• mutation
• over-expression of receptor
• increased autocrine signalling

Question 19

Describe the 2 major classes of EGFR targeted anticancer therapies

Answer 19

• Tyrosine kinase inhibitors (TKIs) - ATP mimetics bind to receptor kinases’s pocket excluding ATP + preventing signal transduction
• Humanised monoclonal antibodies against EGFR extracellular domain that block ligand binding

Question 20

Give an example of a TKI drug used in anticancer therapy

Answer 20

lapatinib

Question 21

Give an example of a monoclonal antibody drug used in anticancer therapy

Answer 21

cetuximab

Question 22

What can the dysregulation of JAK/STAT signalling cause to develop?

Answer 22

• cancer

- immune/inflammatory disorders e.g. psoriasis

Question 23

Name 3 JAK inhibitors developed to treat immune/inflammatory disorders

Answer 23

• Tofacitinib - inhibits JAK1 + 3 inhibitor
• Baricitinib - inhibits JAK1 + 2
• Ruxolitinib - inhibits JAK1 + 2

Question 24

What is an enzyme linked receptor?

Answer 24

transmembrane protein with enzyme activity/direct association with an enzyme

Question 25

How do kinase linked enzymes work?

Answer 25

• bind to ligand leading to a conformational change
• transmitted to TM helix
• enzyme activated
• signalling cascade initiated

Question 26

What 3 things do kinase - linked receptors play a major role in?

Answer 26

cell growth
proliferation
differentiation