Cell Signaling and Signal Transduction Quiz

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Questions and Answers

What is a key characteristic of mutated Ras protein?

  • It is constitutively active due to slow hydrolysis of GTP (correct)
  • It prevents membrane association of RAS
  • It hydrolyzes bound GTP very quickly
  • It binds GTP more effectively than normal Ras

Which approach is suggested as the most favorable current method for targeting RAS?

  • Searching for synthetic lethal interactors
  • Blocking RAS membrane association
  • Direct inhibitors of RAS
  • Targeting RAS downstream effector signaling (correct)

What recent development has sparked hope for RAS-targeting therapies?

  • Breakthroughs in RAS structural biology
  • Renewed interest in developing RAS-inhibitory molecules (correct)
  • Ability to enhance GTP binding in RAS
  • Identification of effective pharmacological inhibitors

Which of the following is NOT mentioned as a potential approach to target RAS?

<p>Increasing GTP hydrolysis rate (D)</p> Signup and view all the answers

What is a widely held perception regarding RAS proteins?

<p>They are considered undruggable (C)</p> Signup and view all the answers

What type of mutations are classified as oncogenes?

<p>Gain of function mutations (D)</p> Signup and view all the answers

What is the role of the SH2 domain?

<p>To recognize phosphotyrosine and nearby residues (B)</p> Signup and view all the answers

Which of the following pathways does Ras primarily activate?

<p>Ras/MAP kinase pathway (A)</p> Signup and view all the answers

Approximately what percentage of human cancers contain mutant versions of RAS genes?

<p>30% (D)</p> Signup and view all the answers

How does Ras mediate signaling for most receptor tyrosine kinases (RTKs)?

<p>As a small GTPase anchored to the plasma membrane (D)</p> Signup and view all the answers

What does Raf do in the MAP kinase signaling cascade?

<p>Activates Mek (C)</p> Signup and view all the answers

Which of these statements best describes the overall signal transduction system mediated by Ras?

<p>It is highly conserved from yeast to humans. (D)</p> Signup and view all the answers

What is one of the main roles of Ras proteins in the cell?

<p>Regulating cell division and differentiation (C)</p> Signup and view all the answers

What is the first step in the MAP kinase signaling cascade initiated by Ras?

<p>Recruitment of Raf to the membrane (C)</p> Signup and view all the answers

Which of the following proteins does MAP kinase (Erk) phosphorylate?

<p>A variety of downstream proteins including gene regulatory proteins (C)</p> Signup and view all the answers

What type of cells were used in the experiments to analyze the effects of oncogenic DNA?

<p>3T3 mouse fibroblasts (B)</p> Signup and view all the answers

What was the outcome of introducing fragmented DNA from cancer cells into 3T3 mouse fibroblasts?

<p>Occasional colonies of abnormally proliferating cells (C)</p> Signup and view all the answers

What characteristic of 3T3 cells made them suitable for studying the effects of oncogenic DNA?

<p>Their capacity to proliferate indefinitely (B)</p> Signup and view all the answers

What was the primary goal of introducing cancer cell DNA into the 3T3 fibroblasts?

<p>To induce uncontrolled cell growth in non-cancer cells (A)</p> Signup and view all the answers

What was concluded about the colonies that formed as a result of the experiments?

<p>They were clones from a single cell incorporating oncogenic DNA. (A)</p> Signup and view all the answers

What is the primary function of KRAS in cancer?

<p>To encode a key signaling protein (D)</p> Signup and view all the answers

What is AMG 510 primarily classified as?

<p>A KRAS(G12C) inhibitor (A)</p> Signup and view all the answers

What effect did AMG 510 have in preclinical analyses?

<p>It led to the regression of KRAS(G12C) tumors (C)</p> Signup and view all the answers

What significant effect did AMG 510 have on the tumor microenvironment?

<p>It resulted in a pro-inflammatory tumor microenvironment (B)</p> Signup and view all the answers

What type of tumors did cured mice reject in the studies?

<p>Isogenic KRAS(G12D) tumors (D)</p> Signup and view all the answers

What was the significance of the FDA approval for adagrasib?

<p>It provided accelerated approval for a RAS GTPase family inhibitor (B)</p> Signup and view all the answers

How do scaffolding proteins influence signaling pathways?

<p>By enhancing mutual interactions in a spatial orientation (C)</p> Signup and view all the answers

Which of the following is NOT a characteristic of some scaffolding proteins?

<p>They can regulate the activity of transcription factors (D)</p> Signup and view all the answers

What is a key function of Rho family GTPases?

<p>Controlling actin and microtubules (B)</p> Signup and view all the answers

What inhibits Rho family GTPases from interacting with its GEF at the plasma membrane?

<p>Guanine nucleotide dissociation inhibitor (GDI) (B)</p> Signup and view all the answers

Which of the following pathways do GPCRs and RTKs predominantly activate?

<p>Overlapping signaling pathways (D)</p> Signup and view all the answers

What role does the SRC homology domain play in signaling?

<p>Mediating protein-protein interactions (B)</p> Signup and view all the answers

Which mutation type is primarily associated with oncogenes?

<p>Gain of function mutation (C)</p> Signup and view all the answers

What is the primary function of SRC in cellular processes?

<p>Signal transduction (A)</p> Signup and view all the answers

What do the SH2 and SH3 domains of SRC primarily facilitate?

<p>Protein-protein interactions (A)</p> Signup and view all the answers

What is the result of a gain-of-function mutation in a proto-oncogene?

<p>Promotes cell growth (A)</p> Signup and view all the answers

What is the relationship between c-src and v-src?

<p>c-src is a proto-oncogene; v-src is its oncogenic counterpart. (C)</p> Signup and view all the answers

How does phosphorylation at Tyr527 affect c-Src's activity?

<p>Inhibits its tyrosine kinase activity (B)</p> Signup and view all the answers

What type of virus was pivotal in the discovery of oncogenes?

<p>Retrovirus (C)</p> Signup and view all the answers

What was discovered about the DNA incorporated by retroviruses like RSV?

<p>It often includes passenger genes from the host. (A)</p> Signup and view all the answers

What kind of kinases are SRC and c-Src classified as?

<p>Non-receptor kinases (A)</p> Signup and view all the answers

What is the designation given to the mutated version of a proto-oncogene?

<p>Oncogene (A)</p> Signup and view all the answers

What role did Peyton Rous play in the study of oncogenes?

<p>He characterized the Rous Sarcoma Virus. (B)</p> Signup and view all the answers

Flashcards

Oncogenic DNA

DNA fragments from cancer cells that cause uncontrolled cell growth.

3T3 cells

Mouse fibroblast cells commonly used in experiments because they proliferate indefinitely in culture.

DNA fragment

A portion of a DNA molecule isolated in experiments to insert into mouse cells.

Clone origin

A group of cells that stem from a single cell and have the same DNA. In experiments, colonies of abnormally proliferating cells.

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Proto-oncogene

Human gene found in cancer cell's DNA fragment.

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Non-receptor tyrosine kinase

An enzyme that adds phosphate groups to tyrosine molecules, but doesn't require a receptor on the cell membrane.

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RTK

Receptor Tyrosine Kinase. Enzymes found in the cell membrane.

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SRC

A non-receptor tyrosine kinase involved in signal transduction.

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SH2 and SH3 domains

Common protein domains in signal transduction proteins; involved in binding to other proteins.

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Oncogene

A gene that has mutated from a proto-oncogene and promotes uncontrolled cell growth.

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Gain-of-function mutation

A mutation that causes a gene to produce a protein with a new, abnormal function, leading to cell growth.

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Rous Sarcoma Virus (RSV)

A retrovirus that causes sarcomas (connective tissue cancers) in chickens.

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v-src

Viral oncogene form of the c-src proto-oncogene.

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c-src

The proto-oncogene that v-src mutated from, found in normal cells.

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Oncoprotein

A protein derived from an oncogene, responsible for uncontrolled cell growth in cancer.

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Constitutively Active Ras

A mutated Ras protein that remains persistently active due to its slow GTP hydrolysis rate, constantly promoting cell growth.

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RAS-Map Pathway

A signaling pathway involved in cell growth and differentiation, mutations in any part can lead to cancer.

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Drugging the Undruggable RAS

The challenge of finding effective drugs to target Ras oncoproteins, traditionally considered difficult to inhibit.

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Targeting RAS Downstream Signaling

A promising approach to treat cancer by targeting signaling pathways downstream of Ras, rather than directly inhibiting Ras itself

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Trans-autophosphorylation

A process where a receptor tyrosine kinase (RTK) activates itself by adding phosphate groups to tyrosine residues on its own structure.

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SH2 domain

A protein domain that recognizes phosphorylated tyrosine residues. This domain is often found in signaling proteins.

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MAP kinase pathway

A signaling pathway that regulates a variety of cellular processes, including cell growth, differentiation, and survival.

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Enzyme-Coupled Receptor

A type of cell surface receptor that activates an enzyme when a ligand binds to it.

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Receptor Tyrosine Kinase (RTK)

A specific type of enzyme-coupled receptor that phosphorylates tyrosine residues on itself and other proteins, initiating signaling pathways.

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KRAS(G12C)

A specific mutation in the KRAS gene where the amino acid glycine at position 12 is replaced with cysteine. This mutation makes the KRAS protein constantly active, promoting uncontrolled cell growth.

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AMG 510

A new drug that specifically targets the KRAS(G12C) mutation. It binds to the mutated protein and blocks its activity, potentially stopping cancer cell growth.

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Covalent Inhibitor

A type of drug that binds to its target molecule (like a protein) very tightly and permanently, disabling it.

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Anti-tumor Immunity

The body's immune system attacking and destroying cancer cells. Immune cells like T cells can recognize and kill tumor cells.

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Immune-Checkpoint Inhibitors

Drugs that block the 'brakes' on the immune system, allowing immune cells to attack cancer cells more effectively.

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Adaptive Immunity

A type of immune response that remembers specific threats (like cancer cells) and mounts a stronger response the next time it encounters them.

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Accelerated Approval

A faster pathway for approving a new drug when there's an unmet medical need and the drug shows promising early results.

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Study Notes

Cell Signaling and Signal Transduction

  • Cell signaling is a communication process between cells
  • Signaling molecules are synthesized and released, travel to the target cell, bind to a receptor, resulting in a conformational change in the receptor
  • The receptor initiates intracellular pathways resulting in changes in cellular function, metabolism, gene expression, shape, and movement
  • Signal transduction pathways involve phosphorylation and dephosphorylation events, which cause changes in protein activity, often enabling or inhibiting ligand binding
  • GTP-binding proteins act as molecular switches, activating or inactivating target proteins
  • Enzyme-coupled receptors are transmembrane proteins with an intrinsic kinase activity or an associated kinase; they are activated by ligand binding, and initiate intracellular signaling cascades
  • RTKs (Receptor Tyrosine Kinases) are the most common enzyme-coupled receptors, and are important in many cellular processes
  • Phosphorylation is a key mechanism for signal transduction
  • Tyrosine phosphorylation is a critical step in activating downstream signaling pathways
  • Phosphorylated tyrosine residues serve as docking sites for signaling proteins, which then relay the signal
  • SH2 and PTB domains are common protein domains involved in binding to phosphorylated tyrosines
  • Signal transduction pathways, specifically the RAS-MAP kinase pathway, activate downstream proteins leading to cellular changes
  • Some components of the pathway have been linked to cancer
  • The pathway is highly conserved from yeast to humans

Oncogenes

  • Oncogenes are genes whose mutations frequently contribute to cancer
  • Proto-oncogenes are normal genes that can mutate into oncogenes through gain-of-function mutations
  • These mutations cause them to promote uncontrolled cell growth
  • Oncogenes often encode proteins, including tyrosine kinases, that play important roles in cell growth or cell cycle
  • Oncogenes were discovered through studies of retroviruses that cause cancers in animals (like Rous Sarcoma Virus)
  • They identified mutated proto-oncogenes that transformed cells even in mammalian hosts

Other Signal Transduction Pathways

  • GPCRs and RTKs activate overlapping signaling pathways, leading to convergence, divergence, and cross-talk. The different signaling pathways can lead to similar or very distinct responses by the cell.
  • Rho family GTPases couple cell surface receptors and regulate actin and microtubules which in turn, regulate cell shape, motility, adhesion, cell cycle progression, gene transcription, and membrane transport
  • Scaffolding proteins that facilitate specific signaling pathways and interactions exist in a variety of cell types

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