E3 Module 8

Question 1

LO - List the steps required for epidermal growth factor receptor signaling

Answer 1

1. ligand binding, receptor dimerization, and kinase activation
2. phosphorylation of RTK cytoplasmic tails
3. Protein binding to RTK phosphotyrosines, and phosphorylation of target proteins
4. Activation of downstream signaling pathways
   –extra–
5. EGF binding induces dimerization and EGFR1 phosphorylation of EGFR2 Tyr residues
6. Conformational change leads to EGFR2 phosphorylation of EGFR1 Tyr residues

Question 2

What type of proteins autophosphorylate the cytoplasmic domain as an initiating step in a phosphorylation - mediated signaling cascade?

Answer 2

Receptor Tyrosine Kinase (RTK)

Question 3

What are the two pathways that insulin signaling initiates and what do they lead to

Answer 3

Ras/MAPK signaling leading to cell growth
PI-3K signaling leading to glucose uptake

Question 4

In EGF receptor signaling: Ras G protein

GRB2
GEF protein
Ras G protein
RasGAP

Answer 4

GRB2 binds first to phosphotyrosine
GEF protein (SOS) activates RAS protein, links RTK to G protein Ras
Ras protein is not heterotrimeric
GTP comes in and GDP leaves, activates downstream signaling pathways
RasGAP stimulates GTPase in Ras to deactivate Ras signaling

Question 5

LO - differentiate between SH2 and SH3 domains

Answer 5

essentially: SH2 binds to and SH3 binds

Question 6

Why are Ras mutations so prevalent in certain types of cancers?

Answer 6

Because a dominant mutation in Ras requires only one mutation to be a gain of function oncogene activation

Question 7

LO - Define the terms oncogene, dominant mutation, recessive mutation, and tumor suppressor

Answer 7

oncogene - cancer causing genes

dominant mutation - requires that only one copy of the gene needs to be mutated to display phenotype, gain-of-function mutation

recessive mutation - requires that both copies of a gene be mutated to display phenotypes, loss-of-function mutation

tumor suppressor gene - associated with recessive mutations? under normal conditions, it functions to inhibit uncontrolled cell proliferation

Question 8

LO - List the steps required for insulin receptor signaling

Answer 8

1. Insulin receptor-mediated activation of PI-3K through phosphorylation of IRS
2. PI-3K phosphorylates PIP2 to form PIP3
3. PDK1 phosphorylates Akt
4. Akt phosphorylates downstream proteins
5. initates a pathway though IRS adaptors in liver cells that stimulate glucose uptake and glycogen synthesis

Question 9

LO - name two primary results from activation of the PI-3K signaling pathway

Answer 9

glucose uptake and glycogen synthesis

Question 10

A new protein is discovered that contains a pleckstrin homology domain. Which of the following is likely to bind to the protein?

Answer 10

PIP3

Question 11

LO - Define apoptosis, death domain, and caspase

Answer 11

apoptosis - programmed cell death
death domain - a region in the cytoplasmic tail of TNF receptors that functions as a protein-protein interaction molecule
caspase - a class of proteins that initiates a proteolytic cascade leading to protein degradation and cell death

Question 12

LO - differentiate between silence of death (SOD) and TNF receptor-associated death (TRAD) domain proteins

Answer 12

SODD - protein that inhibits TNF receptor
TRADD - adaptor protein that binds TNF receptor

Question 13

LO - Identify the key elements of the TNF-mediated apoptotic and cell survival pathways

Answer 13

Apoptic pathway
1. TNF receptor mediated assembly of DD and DED protein complexes
2. autocleavage of procaspase 8
3. CASP8 cleavage of procaspase 3
4. CASP3 cleavage of cellular proteins

Cell survival pathway
1. NIK/RIP - mediated phosphorylation of IKK
2. IKK phosphorylation of IKBa results in activation of p50/p65
3. Active p50/p65 heterodimeric NFkB translocates to the nucleus
4. Increased expression of anti-apoptic genes that inhibit CASP8 and CASP3 activation

Question 14

Which of the following statements is true of procaspase 8?

Answer 14

It is activated by auto-cleavage

Question 15

LO - List the parameters that govern the cell-specific physiologic responses controlled by nuclear receptors

Answer 15

1. ligand bioavailability
2. receptor expression
3. target DNA accessibility

Question 16

LO - differentiate between steroid receptors and metabolite receptors

Answer 16

steroid receptors - bind homodimers to DNA sequences
-bind diff DNA receptors
-head to head
-glucocorticoid, estrogen, androgen, progesteron, aldosterone

metabolite receptors - bind to heterodimers to direct repeat DNA sequences
-diff DNA receptors
-head to tail
-retinoid X, vitamin D, retinoic acid, thyroid hormone, peroxisome

both:
1. bind DNA specifically
2. recruit regulatory protein genes

Question 17

LO - Distinguish between the DNA binding architectures of the homodimeric glucocorticoid receptor and the heterodimeric PPAR-RXR receptors

Answer 17

PPAR is bound to rosiglitazone ligand
RXR is bound to 9-cis-retinoic ligand

Question 18

the flow or _____ of metabolites thorugh catabolic and anabolic pathways is determined by what two primary factors?

Answer 18

1. Availability of substrates
2. Level of enzyme activity
   -enzyme levels (gene transcription, protein synthesis)
   -catalytic activity (allosteric control, covalent modification)
   -compartmentation (subcellular of tissue localization)

Question 19

LO - List the major metabolic pathways in plants and animals

Question 20

LO - distinguish between catabolic and anabolic pathways

Question 21

LO - Define metabolic flux

Answer 21

Metabolic flux refers to the rate at which metabolites are interconverted between reactants and products

Question 22

Metabolism is best defined as…

Answer 22

a collection of biochemical reactions that convert chemical energy into work

Question 23

LO - explain how flux through a pathway changes in response to substrate concentration and enzyme activity

Question 24

LO - Explain how reaction coupling allows an unfavorable ΔG value to be part of a metabolic pathway