Ch5.10

Question 1

What role does the Ras protein play in cell signaling?

Answer 1

The Ras protein functions as a G protein in the downstream signaling cascade, transmitting signals from upstream factors to a downstream target.

Question 2

How do tyrosine kinase receptors affect the Ras signaling pathway?

Answer 2

Tyrosine kinase receptors activate their cytoplasmic domains upon binding with growth factor ligands, which further leads to the activation of the Ras protein via guanine nucleotide exchange factors (GEFs).

Question 3

What are the effects of Ras being in an active state versus an inactive state?

Answer 3

In its active state, Ras binds GTP and emits signals to downstream targets; in its inactive state, it binds GDP and does not transmit signals.

Question 4

What happens to Ras after it hydrolyzes its bound GTP?

Answer 4

After hydrolyzing GTP, Ras returns to its inactive state, binding GDP and ceasing signal emission.

Question 5

How do point mutations in the ras oncogene contribute to cancer?

Answer 5

Point mutations typically lead to amino acid substitutions that impair the GTPase activity of Ras, preventing it from turning off and causing prolonged signaling for cell growth.

Question 6

Why are the codons 12, 13, and 61 significant in ras oncogenes?

Answer 6

These codons are often mutated in tumors, leading to amino acid substitutions that compromise the GTPase function and result in uncontrolled Ras activity.

Question 7

What is the function of the lipid tails on Ras proteins?

Answer 7

The lipid tails anchor Ras proteins to the plasma membrane, allowing them to interact with other signaling molecules.

Question 8

How does the Ras oncoprotein differ from the normal Ras protein?

Answer 8

The Ras oncoprotein often has reduced or absent GTPase activity, leading to continuous signaling even without upstream stimulation.

Question 9

What is the role of the farnesyl-binding protein in the context of Ras?

Answer 9

The farnesyl-binding protein interacts with Ras to facilitate its membrane associations and binding with partner proteins.

Question 10

What is the structural consequence of the mutations in ras oncogenes regarding GTPase activity?

Answer 10

Mutations in specific residues compromise the GTPase activity, affecting Ras’s ability to hydrolyze GTP and terminate signals.

Question 11

In what way does Ras function like a “light switch” in cellular signaling?

Answer 11

Ras behaves like a “light switch” by turning on (activating) with GTP and turning off (inactivating) after hydrolyzing GTP back to GDP.

Question 12

How do mutations in ras improve cellular growth potential?

Answer 12

Mutations that lead to constitutively active Ras result in prolonged signaling for growth and proliferation, giving those cells a survival advantage.

Question 13

Why are mutations in the ras gene considered targets for cancer therapy?

Answer 13

Because they drive uncontrolled cell proliferation, targeting the mutated products of ras may provide therapeutic avenues to halt tumor growth.

Question 14

How many distinct Ras proteins exist in mammalian cells?

Answer 14

There are four distinct Ras proteins, arising from three ras genes, with K-ras specifying a second protein via alternative splicing.

Question 15

What is the role of lipid tails on Ras proteins?

Answer 15

Lipid tails (farnesyl, palmitoyl, or geranylgeranyl) enable Ras proteins to anchor to cytoplasmic membranes, particularly the plasma membrane.

Question 16

How does the H-Ras protein interact with membranes?

Answer 16

H-Ras has a complex membrane interaction: its palmitate moiety directly inserts into cytoplasmic membranes, while its farnesyl group binds to a specialized farnesyl-binding protein.

Question 17

What makes Ras protein behavior similar to heterotrimeric G-proteins?

Answer 17

Like G-proteins, Ras binds and hydrolyzes guanosine nucleotides and cycles between active and inactive states by binding GDP or GTP.

Question 18

Describe the cycle of Ras protein activation and deactivation

Answer 18

Ras binds GDP when inactive, receives a stimulatory signal to release GDP, acquires GTP, shifts to an activated configuration, and then cleaves GTP to return to its inactive state.

Question 19

What is the metaphorical description of Ras protein function?

Answer 19

Ras functions like a “light switch” that automatically turns itself off after a predetermined time.

Question 20

How do mitogenic signals activate Ras?

Answer 20

Mitogenic signals activate a guanine nucleotide exchange factor (GEF) for Ras, which induces the protein to replace GDP with GTP.

Question 21

What role do GTPase-activating proteins (GAPs) play?

Answer 21

GAPs can encourage Ras to hydrolyze its bound GTP, helping to terminate the signaling period.

Question 22

What was unique about the Ras oncoprotein from Harvey sarcoma virus?

Answer 22

This oncoprotein could bind GTP but had lost virtually all GTPase activity, preventing it from turning off and stopping signal emission.

Question 23

Why are Ras oncoproteins problematic for cell growth?

Answer 23

They emit growth-stimulating signals for extended or indefinite periods, flooding the cell with continuous growth signals.

Question 24

Which codons are most frequently mutated in ras oncogenes?

Answer 24

Mutations most frequently occur in codons 12, 13, and 61, with the majority affecting codon 12.

Question 25

Why do these specific codons matter in ras mutations?

Answer 25

These codons are located around the cavity where Ras’s GTPase catalytic activity operates, and mutations here compromise GTPase function.

Question 26

Why are large-scale alterations of ras proto-oncogenes ineffective for cancer?

Answer 26

Large deletions would eliminate Ras protein function entirely, rather than enhancing its signal-emitting capabilities.

Question 27

What makes a Ras mutation potentially cancerous?

Answer 27

A mutation that leaves signal-emitting powers intact while inactivating the GTPase negative-feedback mechanism.

Question 28

Why do only certain Ras mutations appear in tumor cells?

Answer 28

Only mutations that confer a substantial growth advantage are selected and found in tumor cells.

Question 29

How do the lipid groups differ among Ras proteins?

Answer 29

Ras proteins can have farnesyl, palmitoyl, or geranylgeranyl groups (or combinations of these) at their C-termini.

Question 30

What is the significance of missense mutations in ras oncogenes?

Answer 30

Missense mutations cause amino acid substitutions that can compromise GTPase function without completely eliminating protein activity.

Question 31

How do Ras proteins transduct signals?

Answer 31

Ras acts as a signal-transducing protein, receiving signals from upstream in a cascade and passing them to downstream targets.

Question 32

What prevents most point mutations from causing cancer?

Answer 32

Most point mutations either eliminate Ras protein function or do not provide a significant growth advantage.

Question 33

How does the Ras protein’s structure relate to its function?

Answer 33

The structure around residues 12, 13, and 61 is critical for GTPase activity and signal regulation.

Question 34

What determines a successful cancer-causing Ras mutation?

Answer 34

A mutation that maintains signal-emitting capabilities while disrupting the negative-feedback GTPase mechanism.

Question 35

How do Ras proteins interact with other signaling molecules?

Answer 35

Through membrane anchoring and specialized binding proteins like the farnesyl-binding protein.

Question 36

Why are specific residues (12, 13, 61) crucial in Ras protein function?

Answer 36

These residues are located in the cavity controlling GTPase catalytic activity.

Question 37

What makes the Ras protein’s signaling mechanism unique?

Answer 37

Its ability to automatically switch between active and inactive states through GTP binding and hydrolysis.

Question 38

How do GAPs contribute to Ras protein regulation?

Answer 38

GAPs encourage GTP hydrolysis, helping to terminate the Ras protein’s signaling state.

Question 39

What evolutionary mechanism explains the selection of specific Ras mutations?

Answer 39

Only mutations providing a clear proliferative advantage are retained in tumor cells.