Week 3

Question 1

What does tyrosine phosphorylation do?

Answer 1

Protein tyrosine phosphorylation (PTP) is an important posttranslational modification that controls the cell signaling involved in the regulation of a variety of biological processes, including cell growth, proliferation, differentiation, migration, survival, and death

Question 2

What is the relationship between RTKs and adapter proteins?

Answer 2

Adaptor proteins serve an important scaffolding function that facilitates key signaling transduction events downstream of RTKs

Question 3

What is Ret mutation?

Answer 3

The most common genetic cause of Hirschsprung disease, a disorder that causes severe constipation or blockage of the intestine.

Question 4

What is the link between the RET gene and disease?

Answer 4

Mutations in the RET gene are the most common genetic cause of Hirschsprung disease, a disorder that causes severe constipation or blockage of the intestine. More than 200 RET gene mutations are known to cause this condition.

Question 5

What are the main functions of GPCRS?

Answer 5

Mediate most cellular responses to hormones and neurotransmitters, as well as being responsible for vision, olfaction and taste.

Question 6

What second messengers do GPCRs send signals to?

Answer 6

Cyclic AMP (cAMP) exclusively from the plasma membrane

Question 7

What do drugs that target GPCRs include?

Answer 7

Both agonists and antagonists that are used in the treatment of diseases of nearly every major organ system, including the central nervous system (CNS), cardiovascular, respiratory, metabolic and urogenital systems

Question 8

How do GPCRs work in cancer?

Answer 8

Modulate the processes such as proliferative signaling, replicative immortality, evasion of growth suppressors, resistance to apoptosis, initiation of angiogenesis, and activation of invasion and metastasis that are identified as the hallmarks of cancer

Question 9

What is cell surface receptor signaling pathway?

Answer 9

The pathway begins with binding of an extracellular ligand to a cell surface receptor, or for receptors that signal in the absence of a ligand, by ligand-withdrawal or the activity of a constitutively active receptor

Question 10

What causes cancer?

Answer 10

Damage to the DNA in your cells.

Question 11

What is a tumour suppressor gene?

Answer 11

Gene that regulates a cell during cell division and replication

Question 12

What are the four major mechanisms of tumour suppressor loss?

Answer 12

• inhibition of cell division
• induction of apoptosis
• DNA damage repair
• inhibition of metastasis.

Question 13

What are proto-oncogenes?

Answer 13

A group of genes that cause normal cells to become cancerous when they are mutated

Question 14

What is the role of oncogene?

Answer 14

They regulate cell proliferation, growth, and differentiation, as well as control of the cell cycle and apoptosis.

Question 15

What does oncogene addiction describe?

Answer 15

The dependency of certain tumor cells on a single activated oncogenic protein or pathway to maintain their malignant properties, despite the likely accumulation of multiple gain- and loss-of-function mutations

Question 16

What do cancer cells do to tyrosine kinases?

Answer 16

Blocking them may help keep cancer cells from growing

Question 17

What does the EGFR family play a role in?

Answer 17

Regulating cell proliferation, survival, differentiation and migration

Question 18

What does the loss of EGFR receptor regulation underlie?

Answer 18

Many human diseases, most notably cancer

Question 19

How is EGFR activated?

Answer 19

According to the “ligand-induced dimerization model”, EGFR is activated by the ligand-induced dimerization of the receptor monomer, which brings intracellular kinase domains into close proximity for trans-autophosphorylation to initiate downstream signaling cascades.

Question 20

What is EGFR dimerisation?

Answer 20

Dimerization is essential to enable the intracellular kinase domain of EGFR to become activated.

Question 21

How does EGFR signal?

Answer 21

Epidermal growth factor receptor (EGFR) signaling pathways leading to G1/S cell cycle progression activated by EGF activation.

Question 22

How does the adaptor protein Grb2 function?

Answer 22

Binds phosphotyrosines in the epidermal growth factor (EGF) receptor (EGFR) and thereby links receptor activation to intracellular signaling cascades.

Question 23

What are pseudokinases?

Answer 23

The catalytically defective counterparts of conventional, active protein kinases and have been attributed functions as protein interaction domains acting variously as allosteric modulators of conventional protein kinases and other enzymes, as regulators of protein trafficking or localisation, as hubs to nucleate assembly of signalling complexes, and as transmembrane effectors of such functions

Question 24

What does the subcellular localisation of RAS GTPases define?

Answer 24

The operational compartment of the EGFR-ERK1/2 signaling pathway within cells

Question 25

What pathways are activated with EGFR?

Answer 25

The RAS/RAF/MAPK, AKT, and JAK/STAT pathways downstream of EGFR play integral roles in cell migration, proliferation, and survival, respectively.

Question 26

What is the combination of anti-EGFR and MEK inhibitor able to prevent?

Answer 26

The onset of resistance to anti-EGFR monoclonal antibodies in KRAS-wild type colorectal cancer (CRC), while the same combination reverts anti-EGFR primary resistance in KRAS mutated CRC cell lines

Question 27

What is EGFR?

Answer 27

A transmembrane protein that is a receptor for members of the epidermal growth factor family of extracellular protein ligands

Question 28

How is EGFR signalling turned off?

Answer 28

By blocking EGFR binding sites on the extracellular domain of the receptor or by inhibiting intracellular tyrosine kinase activity

Question 29

What is the role of PTP1B?

Answer 29

Its purpose is to downregulate EGFR signaling through dephosphorylation of tyrosine residues

Question 30

What does the activation of EGFR lead to?

Answer 30

Internalization of the receptor and trafficking to the early endosomal compartment of the cell

Question 31

What are the three independent sources that determine EGFR activation?

Answer 31

• Ligand-binding-driven EC dimerization
• Proximity-driven dimerization by clustering on a limited number of lipid rafts
• Direct asymmetric KD dimer formation with enhanced affinity

Question 32

What is the most commonly expressed/overexpressed membranous oncogenic protein in cancer?

Answer 32

EGFR

Question 33

What is the function of ErbB2?

Answer 33

Genetic data demonstrated that erbB2 is required for normal embryonic development of neural crest-derived cranial sensory neurons.

Question 34

What is a mutation in the EGFR gene a biomarker for?

Answer 34

Non-small cell lung cancer

Question 35

What treatment do most lung cancers with activated EGFR respond to?

Answer 35

Gefitinib

Question 36

Will lung cancer treatment improve?

Answer 36

Lung cancer death rates have fallen sharply in the US in recent years, while survival rates have improved. This is largely due to newer treatments, according to a study led by researchers from the US National Cancer Institute (NCI) and published recently in the New England Journal of Medicine

Question 37

What is the frequency of EGFR gene amplification in gliblastomas?

Answer 37

Observed in approximately 40% of tumors