MODULE 8: Chapter 8.3

Question 1

What is the function of receptor tyrosine kinases (RTKs)?

Answer 1

Transmit extracellular signals by ligand activation of an intrinsic tyrosine kinase function

Question 2

What does EGFR stand for?

Answer 2

Epidermal growth factor receptor

Question 3

What is the role of Akt in RTK signaling?

Answer 3

Enzyme with kinase activity, also known as protein kinase B (PKB)

Question 4

Fill in the blank: The intrinsic kinase of RTKs phosphorylates ______ residues.

Answer 4

tyrosine

Question 5

What type of proteins do RTK target proteins often serve as?

Answer 5

Adaptor proteins

Question 6

What are the two best-characterized RTK signaling pathways?

Answer 6

Epidermal growth factor receptor (EGFR) and insulin receptor

Question 7

What is the main consequence of RTK signaling pathways?

Answer 7

Increased cell division

Question 8

How many amino acids does epidermal growth factor (EGF) have?

Answer 8

53

Question 9

What structural feature does EGF possess?

Answer 9

Three disulfide bridges

Question 10

What is the function of the SH2 domain?

Answer 10

Binds phosphotyrosine residues

Question 11

True or False: GRB2 is an adaptor protein that binds to pY residues.

Answer 11

True

Question 12

What does RasGAP do?

Answer 12

Stimulates the intrinsic GTPase activity in Ras

Question 13

What is the first kinase in the MAP kinase pathway?

Answer 13

Raf

Question 14

Fill in the blank: The MAP kinase pathway is involved in ______ regulation.

Answer 14

gene expression

Question 15

What type of activity does Ras possess?

Answer 15

GTPase activity

Question 16

What is the role of MEK in the MAP kinase pathway?

Answer 16

Phosphorylates the third kinase, ERK

Question 17

What is the final cellular response to the MAP kinase signaling pathway?

Answer 17

Increased rates of cell division

Question 18

What do defects in RTK signaling pathways often lead to?

Answer 18

Human diseases, including cancer

Question 19

What type of mutations are commonly linked to human cancers?

Answer 19

Somatic mutations in cell signaling genes

Question 20

What is the primary function of the enzyme phosphoinositide 3-kinase (PI3K)?

Answer 20

Key role in insulin signaling

Question 21

What is the significance of the term ‘mitogen’ in the context of MAP kinase signaling?

Answer 21

A compound that activates mitosis

Question 22

What is the relationship between GRB2 and SOS?

Answer 22

GRB2 recruits SOS to activate Ras

Question 23

What happens to activated ERK in the signaling pathway?

Answer 23

Translocates to the nucleus to regulate gene expression

Question 24

What are the two major types of somatic mutations found in humans?

Answer 24

Gain-of-function oncogene mutations and loss-of-function oncogene mutations

Gain-of-function mutations are also called dominant mutations, while loss-of-function mutations are recessive.

Question 25

What is the significance of oncogenes in cancer?

Answer 25

Oncogenes are cancer-causing genes that result from mutations in normal cell signaling genes. ## Footnote The discovery of oncogenes was made by J. Michael Bishop and Harold E. Varmus.

Question 26

What is the role of the retinoblastoma gene?

Answer 26

It is a tumor suppressor gene that inhibits uncontrolled cell proliferation. ## Footnote Inactivating mutations in this gene lead to retinoblastoma cancer.

Question 27

True or False: A dominant gain-of-function mutation requires both gene copies to be mutated to cause cancer.

Answer 27

False ## Footnote A dominant mutation only requires one copy to lead to a disease phenotype.

Question 28

What is the most common type of cancer mutation?

Answer 28

Dominant gain-of-function mutations ## Footnote These mutations result in new activity in the cell, such as uncontrolled growth.

Question 29

What is an example of a common oncogenic mutation in Ras proteins?

Answer 29

Missense mutations that decrease the intrinsic GTPase activity. ## Footnote Common mutations include G12D, G12V, and G12R.

Question 30

Fill in the blank: The insulin receptor consists of an ______ complex.

Answer 30

α2β2 tetrameric ## Footnote The α and β subunits are linked by disulfide bonds.

Question 31

What are the two major downstream pathways controlled by insulin receptor signaling?

Answer 31

Increased glucose uptake and glycogen synthesis, and stimulation of cell division. ## Footnote These pathways are activated through IRS and Shc proteins.

Question 32

What triggers the activation of the insulin receptor?

Answer 32

Binding of a single insulin molecule ## Footnote This binding induces a conformational change that activates the receptor.

Question 33

What are IRS proteins and their role in insulin signaling?

Answer 33

Insulin receptor substrate proteins that bind to phosphotyrosine residues in the insulin receptor and activate downstream signaling pathways. ## Footnote IRS-1 is predominant in muscle cells, while IRS-2 is predominant in liver cells.

Question 34

What is the function of PI3K in insulin signaling?

Answer 34

It phosphorylates PIP2 to produce PIP3, leading to increased glucose uptake and glycogen synthesis. ## Footnote PI3K is activated by tyrosine-phosphorylated IRS proteins.

Question 35

What is the role of PTEN in PI3K signaling?

Answer 35

PTEN terminates PI3K signaling by removing the phosphate from PIP3 to regenerate PIP2. ## Footnote Mutations in PTEN can lead to uncontrolled cell growth in tumors.

Question 36

What is the significance of negative cooperativity in insulin receptor signaling?

Answer 36

Binding of one insulin molecule inhibits the binding of a second insulin molecule. ## Footnote This is different from positive cooperativity observed in hemoglobin.

Question 37

What are the three tyrosine residues that must be autophosphorylated in the insulin receptor to activate its substrate kinase activity?

Answer 37

pY1158, pY1162, pY1163 ## Footnote These residues are part of the tyrosine kinase domain.

Question 38

What happens to the MAP kinase pathway when the insulin receptor signaling is activated?

Answer 38

It stimulates altered gene expression and cell division. ## Footnote This occurs through Shc-mediated activation of the pathway.

Question 39

What is a common characteristic of gain-of-function mutations in cancer cells?

Answer 39

They promote cell growth in the absence of regulatory signals that control cell growth. ## Footnote These mutations can affect both PI3K and MAP kinase pathways.

Question 40

What activates the MAP kinase signaling pathway?

Answer 40

Function mutations through Ras mutations

Question 41

Which domains in signaling proteins bind to membrane-associated lipids?

Answer 41

Pleckstrin homology (PH) domains

Question 42

What is the role of PIP3 in the insulin signaling pathway?

Answer 42

Serves as a docking site for signaling proteins containing PH domains

Question 43

Name two proteins in the insulin signaling pathway that bind to PIP3.

Answer 43

* Phosphoinositide-dependent kinase-1 (PDK1) * Akt (protein kinase B)

Question 44

What is the function of Akt in liver cells?

Answer 44

Initiates downstream signaling pathways resulting in glucose import and glycogen synthesis

Question 45

How does insulin signaling affect blood glucose levels?

Answer 45

Lowers blood glucose levels by removing glucose from circulation

Question 46

What is the opposite effect of insulin signaling in liver cells?

Answer 46

Glucagon signaling increases glucose export

Question 47

What are the four types of binding domains required for EGF and insulin signaling?

Answer 47

* SH2 domains * SH3 domains * PTB domains * PH domains

Question 48

True or False: SH2 domains bind to phosphotyrosine residues.

Answer 48

True

Question 49

Fill in the blank: A glycine residue at position 12 of the G protein Ras is only active in the presence of _______.

Answer 49

[growth factors]

Question 50

What is an oncogene?

Answer 50

A mutated version of a normal gene that can cause cancer

Question 51

What type of mutation requires only one copy of the gene to be mutated to display a phenotype?

Answer 51

Dominant mutation

Question 52

What is a recessive mutation?

Answer 52

Requires both copies of the gene to be mutated to display a phenotype

Question 53

What is the role of the tumor suppressor gene?

Answer 53

Inhibits uncontrolled cell proliferation

Question 54

What does the phosphotyrosine binding (PTB) domain bind to?

Answer 54

Phosphotyrosine residues on target proteins

Question 55

What is the function of the insulin receptor substrate (IRS)?

Answer 55

Binds to phosphorylated insulin receptors through phosphotyrosine binding domains

Question 56

What does the pleckstrin homology (PH) domain bind to?

Answer 56

PIP3 in the plasma membrane

Question 57

What is the function of phosphoinositide-dependent kinase-1 (PDK1)?

Answer 57

Binds to PIP3 and phosphorylates Akt

Question 58

What does Src kinase homology-2 (SH2) domain bind to?

Answer 58

A specific amino acid sequence containing a phosphotyrosine residue

Question 59

What is the role of growth factor receptor–bound 2 (GRB2)?

Answer 59

An SH2/SH3 adaptor protein that binds to the EGF receptor

Question 60

What does Src kinase homology-3 (SH3) bind to?

Answer 60

Specific proline-rich sequences

Question 61

What are mitogen-activated protein kinases (MAP kinases) involved in?

Answer 61

Activating a phosphorylation cascade leading to increased rates of cell division

Question 62

What is phosphatidylinositol-3,4,5-trisphosphate (PIP3)?

Answer 62

A glycolipid that recruits proteins with a PH domain to the plasma membrane

Question 63

What does phosphatase and tensin homolog (PTEN) do?

Answer 63

Removes a phosphoryl group from PIP3 to regenerate PIP2