Growth Factors, Receptors, And Cancer - Quiz 3

Question 1

Intercellular comunication

Answer 1

• Critical to embryonic development, tissue differentiation, and systemic responses to wounds and infections.
  These are initiated by Growth Factors

Question 2

Growth Factors

Answer 2

• Secreted protein that is able to stimulate the growth and/or proliferation of a cell by binding to a specific cell-surface receptor displayed by that cell.

Question 3

Mitogen

Answer 3

An agent that provokes cell proliferation

Question 4

Secretome

Answer 4

• The collection of proteins that are released by a cell into the extracellular space under specific physiological conditions or states or differentiation, often focused on signaling proteins

Question 5

Scratch/wound healing assay

Answer 5

• A scratch wound healing assay is used to measure basic cell migration parameters. A “wound” is created in a cell mono layer by scratching with a pipette tip. Cell migration into the wound space is measured.

Question 6

Platelet-derived growth factor (PDGF)

Answer 6

• A potent mitogen for mesenchymal cell types
• Produced and released by platelets (and other cell types) upon activation
• Five different isoforms of PDGF

Question 7

Platelet-derived growth factor receptor (PDGFR)

Answer 7

• Cell surface receptor for PDGFs
• Receptor tyrosine kinase (RTK)
• Two types of PDGFRs

Question 8

What happens if PDFG or serum is not present?

Answer 8

Cells are not able to proliferate

Question 9

What is cancer?

Answer 9

It is a disease of aberrant signal processing.

Question 10

Steps of signal transduction

Answer 10

1. Receptor
2. Transduction
3. Response
4. Signal Termination

Question 11

Molecules that are involved in cell communication

Answer 11

• Signaling molecules
  
  • Ligands
• Receptor (e.g., RTK)
• Adaptor proteins (e.g., Grb2)
• Relay/signal processing molecules
  - SOS, Ras, Raf, MEK, ERK
  - Scaffolding proteins
• Response/ output
  - activation of transcription factors

Question 12

Kinase

Answer 12

• An enzyme that removes the y phosphate from ATP and covalently attaches the phosphate moiety to substrate molecules, often but not exclusively to proteins.

Question 13

What side chains of amino acid residues do protein kinases attach phosphates?

Answer 13

• Serine/threonine kinases
• Tyrosine kinases
  - Receptor tyrosine kinase
  - Non-receptor tyrosine kinase

Question 14

What is SRC

Answer 14

• non-receptor tyrosine
• phosphoprotein
• can phosphorylate more than 50 distinct substrates

Question 15

Phosphoprotein

Answer 15

a protein to which one or more phosphate groups have been covalently attached

Question 16

Interactome

Answer 16

a set of protein-protein interactions

Question 17

Receptors for growth factors are enzyme-linked, transmembrane receptors

Answer 17

• Receptor tyrosine kinase (RTKs)
• TGF - beta (serine-threonine kinases)
• JAK-STAT (Janus kinase)

Question 18

GF receptor domains

Answer 18

• Ectoderm (extracellular domain): ligand binding
• Transmembrane domain
• Juxtamembrane domain
• Cytoplasmic domain

Question 19

Juxtamembrane domain

Answer 19

• Mutations in this domain are a common mechanism by which RTKs become constitutively activated and drive cancer progression.

Question 20

Signaling through RTKs

Answer 20

• Receptor dimerization, ligand binding, and transphosphorylation
• RTKs can exist as monomers in an inactive state or as inactive predimers or larger scale clustering

Question 21

Alterations/ mutations that result in deregulation of receptors

Answer 21

• Mutations affecting structure
• Overexpression
• Creation of autocrine signaling loop
• Gene fusions

Question 22

Mutations affecting structure include …

Answer 22

• truncation of ectodomain
  - can emit mitogenic signals constitutively
• point mutation (amino acid substitutions)

Question 23

Creation of an autocrine signaling loop

Answer 23

• In many types of cancer, tumor cells acquire the ability to make a growth factor for a receptor that they naturally display

Question 24

Gene fusion causing constitutively dimerized receptors

Answer 24

• Ros is an RTK
• Fig is a protein that dimerizes spontaneously
• In glioblastoma, the reading frame of the ROS ectodomain is fused to the FIG reading frame
• The Ros-Fig fusion protein dimerizes resulting in constitutive, GF-independant dimerization and signaling.

Question 25

JAK/STAT signaling pathway

Answer 25

• Janus kinase/signal transducer and activator of transcription
• pathway activated by cytokines, interferon, and some hormones
• Canonical signaling and. non-canonical deviations

Question 26

JAKs are:

Answer 26

• Non-receptor tyrosine kinases
• noncovalently associated with cytokine receptors

Question 27

Canonical Jak/STAT signaling

Answer 27

1. Cytokines bind to the receptors bringing JAKs into proximity
2. JAKs transphosphorylate and phosphorylate the C-terminal tails of the receptor creating a docking site for STAT monomers
3. STATs are phosphorylated, then they dimerize, translocate to the nucleus, bind to DNA, and induce expression of target genes

Question 28

TGF-β receptors

Answer 28

• Transforming growth factor-β (TGF-β) type I and type II receptors
  ● Serine-threonine kinases

Question 29

Wnt/β-cateninsignalingpathway

Answer 29

● No Wnt signal: a complex of AXIN and APC allows GSK-3β to phosphorylate β-catenin.
This marks β-catenin for degradation by ubiquitin-dependent proteolysis.
● Wnt signal: Wnt ligand binds to the Frizzled receptors and the LRP co-receptor. Dishevelled is recruited by the receptor and prevents the destruction β-catenin