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PHRM836 > Exam 2 General Knowledge 10-18 > Flashcards

Exam 2 General Knowledge 10-18 Flashcards

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1
Q

What is the purpose of signal transduction?

A

To coordinate cell metabolism, growth, and development
To ensure homeostasis among tissues and organs
The respond to external stimuli (light,pressure, and heat)

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2
Q

What is the pathway of signal transduction cascade?

A

A ligand binds to receptor
Transduction happens which relays the message
There is a response

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3
Q

Does cAMP go through amplification?

A

NO

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4
Q

What is juxtacrine signaling?

A

Cell-cell contact

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5
Q

What is endocrine signaling?

A

Hormones secreted into the bloodstream
They have a low concentration
A high-affinity receptor, response time minutes to hours

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6
Q

What is paracrine signaling?

A

Secreted ligands target nearby cells
High local concentration
Low affinity receptor, response time is seconds to minutes

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7
Q

What is synaptic signaling?

A

Neuronal signaling
Synapse between neuron cells/very short distance
Very high local concentration
Very low affinity receptor happens in milliseconds
A special type of paracrine signaling

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8
Q

What is autocrine signaling?

A

Sender and target are the same cell
Response time similar to paracrine (seconds to minutes)

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9
Q

What are the secreted molecules of signaling?

A

They are the first messangers and ligands for receptors

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10
Q

What are intracellular receptors?

A

Only used for steroid hormones, thyroid hormones, or vitamins. They need to be hydrophobic

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11
Q

Can intracellular hormones control gene expression?

A

Yes, they form a dimer and eventually get into the nucleus and can control gene expression

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12
Q

What type of motif is the thyroid nuclear receptor?

A

A zinc finger

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13
Q

Where is the hormone bound on the structure of the thyroid receptor-DNA complex?

A

The middle part of the bottom part of the motif, they cause a conformational change which makes it become a dimer

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14
Q

What are the major cell-surface receptors?

A

Ligand-gated ion channels
Enzyme-linked or catalytic receptors
Cytokine family receptors
GPCRs

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15
Q

What are secondary messangers?

A

They are small molecules that are not proteins that are a cause of the first messengers. They happen intracellularly.

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16
Q

What does downstream signaling control?

A

Protein phosphorylation

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17
Q

What does protein phosphorylation do?

A

Induce conformational change
Promote or disrupt protein-protein interaction
It also causes large assemblies of proteins called scaffold, adaptor or anchoring proteins

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18
Q

Second way to control downstream signaling controls

A

GTP-binding regulatory proteins

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19
Q

GTP-binding regulatory proteins

A

GTP causes a signaling, get dephosphorylated then turns off but can get restarted again by GTP re-entering
GTP BOUND STATE IN ON

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20
Q

Which form of GTP-binding regulatory proteins interacts strongly with downstream signaling proteins?

A

The on state or the GTP bound form

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21
Q

What is Ras?

A

A type of monomeric G-proteins that causes cell proliferation and if a mutation occurs then it will most likely cause cancer

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22
Q

What are the two ways to terminate a signal?

A

Changing the amount of message (SERT)
Receptor loss or desensitization (lower response to the same agonist concentration)

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23
Q

Ligand gated ion channels are usually involved in what type of signaling?

A

Neuronal signaling

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24
Q

Besides receptor internalization, another way to terminate the signaling form receptor tyrosine kinase could be?

A

Protein phosphatase as part of a protein phosphorylation cycle

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25
Receptor tyrosine kinase activates what well known signaling cascade?
Ras / MAP kinase signaling cascade
26
What is Ras-activating protein
GEF or guanine exchange factor
27
What is Ras?
Ras is a monomeric G protein which turns GDP into GTP
28
Activated Ras binds and activated MAP3K which signals the cascade of what
MAP-kinase-kinase-kinase MAP-kinase-kinase MAP-kinase -> to do a signal
29
Adaptor protein of Ras
Grb2
30
What does GPCRs have activity and amplification wise
GEF activity and Big amplification
31
Which subunit of the trimeric G protein is similar to the structure of monomeric G protein
G alpha
32
What does pleiotropic mean?
The same cytokine can have different target cells and receptors with different biological outcomes
33
Are cytokines redundant?
Yes, different cytokines can produce the same effect
34
What is cascade effect?
Cytokines can stimulate the production of other cytokines
35
What are chemokines
Cause cell migration during development, immune response, inflammation and cancer
36
What are chemokine receptors?
GPCRs
37
What do interferons do?
They interfere with viral replication also in regulation of immune response
38
Are cytokines a good therapeutic target?
yes, because of their anti-inflammatory pathways with could help with pathological pain from inflammation such as peripheral nerve injury
39
What happens when cytokine receptors are overexpressed?
They can cause tumor cells and are being looked at therapeutically to help suppress this
40
What are the cytokine receptors?
1. Immunoglobulin family (Ig) 2. Hemopoietic growth factor (type 1) family 3. Interferon (type 2) family 4. Tumor necrosis factors (TNF) (type 3) 5. GPCRs 6. Interleukin-17 receptor (IL-17R) family
41
How many chemokines are in the human family and how many receptors
There are 46 protein chemokines and 23 GPCR receptors
42
Cytokine receptors
They have cross-reactivity so they can have different cytokines bind to the same receptor
43
Type 1 cytokine receptor intracellular domain (spider)
A huge complex inside of the cell with up to 600 residues, they are very atypical
44
how to terminate a signal
rapid reducing the message by use of SERT breakdown of enzymes by acetylcholine esterase less signal over time but with the same concentration
45
RTKs
receptor tyrosine kinases that leads to phosphorylation of downwards signaling
46
What activates Ras/MAP kinase?
RTK receptor tyrosine kinases
47
When Ras is activated what does it do?
Activates cell proliferation, migration, transformation, survival but mutations can lead to cancer
48
What are the three Ras genes?
HRas, Kras, Nras
49
what are cytokines?
small proteins used to control growth and immune system cells to execute inflammation responeses
50
pleiotropic.....
the same cytokine can bind to different receptors and have a different effect
51
redundant
when different cytokines produce a similar effect
52
cascade effect
cytokines can stimulate the production of other cytokines
53
TNF-a
tumor necrosis factor that gets released upon infection from macrophages
54
Chemokines do what?
cell migration and theyre also called CXCL8
55
What is Icam and LFA-a
Where leukocytes go through rolling adhesion and stop because of the extracellular receptor Icam
56
Siltuximab
cancer drug which inhibits IL-6
57
Tocilizumab and Sarilumab
cancer drugs which inhibits IL-6 receptor
58
Adaptive immunity
Remember and specific respond slower (B and T-cells)
59
Innate immunity
respond much faster non-specific and have no memory
60
What are the ways that GPCRs terminates signaling
Phosphorylation of G-protein coupled receptor b-arrestin internalization in clathrin-coated pit recycling or degradation
61
Gproteins and who they effect in GPCRs
Gs and Gi both effect adenylyl cyclase -> cAMP -> PKA Gq effects phospholipase C - Diacylglycerol OR IP3 -> PKC OR IP3 receptor -> CALCIUM
62
CaM or calmodulin does what?
A small protein that binds to excess calcium and releases it
63
ori?
Origin of replication
64
What is topoisomerase do?
Essential for termination
65
What is p53?
A tumor suppressant protein
66
What do methotrexate and 5-flurouracil do?
They inhibit DNA replication to make sure the tumor cant keep growing
67
BCR-ABL what is it?
Causes cancer and shorten chromosome length
68
What is chromatin?
a long chain of wound up dna histones
69
epigenetics
post-transloational modifications of histones
70
What do HATs do?
They open up dna on a histone (acetylation)
71
What do HDACs do?
They wind the dna back up on the histone (deacetylation)
72
Transcription
Makes mRNA
73
Translation
mRNA goes through a ribosome and adds codons
74
Chaparone
Helps fold DNA
75
Misfolded proteins are called what?
Aggregation
76
Posttranslational modifications (PTMs) do what?
They add complexity to the proteome
77
What do large aggregates cause?
Can cause alzheimers, parkinsons, or hunningtons
78
Ubiquititin-proteasome proteolysis
A process that is targeted for degredation as part of cellular function
79
Lysosomal degredation
membrane-bound organelles containing proteases that can degredate exogenous proteins or aged/damaged organelles
80
Autophagy
Self engulfing process that gets rid of trash / defective organelles
81
Defective autophagy casues
alzheimers
82
Targets protein degredation by the proteasome, whats it made of
2x 19s complex and 1x 20s core complex
83
Ubiquitin-proteqsomal system process
E1 (activating), E2 (conjugating), E3 (ligase),need at least 4 ubiquitin molecules to be able to degrade
84
What activity does the 20s proteasome have?
Trypsin, caspase and chymotrypsin
85
Oxidative stress and proteasome
disassembles the 19s complex and leaves the 20s complex to degrade oxidized proteins
86
degron
recognition sequence or structure for an E3 ligase
87
Bortezomib
A cancer drug, the first proteasome inhibitor

PHRM836 (2 decks)

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