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PHRM836 > Exam 2 General Knowledge 10-18 > Flashcards

Exam 2 General Knowledge 10-18 Flashcards

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
Q

Receptor tyrosine kinase activates what well known signaling cascade?

A

Ras / MAP kinase signaling cascade

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26
Q

What is Ras-activating protein

A

GEF or guanine exchange factor

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27
Q

What is Ras?

A

Ras is a monomeric G protein which turns GDP into GTP

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28
Q

Activated Ras binds and activated MAP3K which signals the cascade of what

A

MAP-kinase-kinase-kinase
MAP-kinase-kinase
MAP-kinase -> to do a signal

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29
Q

Adaptor protein of Ras

A

Grb2

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30
Q

What does GPCRs have activity and amplification wise

A

GEF activity and Big amplification

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31
Q

Which subunit of the trimeric G protein is similar to the structure of monomeric G protein

A

G alpha

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32
Q

What does pleiotropic mean?

A

The same cytokine can have different target cells and receptors with different biological outcomes

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33
Q

Are cytokines redundant?

A

Yes, different cytokines can produce the same effect

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34
Q

What is cascade effect?

A

Cytokines can stimulate the production of other cytokines

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35
Q

What are chemokines

A

Cause cell migration during development, immune response, inflammation and cancer

36
Q

What are chemokine receptors?

A

GPCRs

37
Q

What do interferons do?

A

They interfere with viral replication also in regulation of immune response

38
Q

Are cytokines a good therapeutic target?

A

yes, because of their anti-inflammatory pathways with could help with pathological pain from inflammation such as peripheral nerve injury

39
Q

What happens when cytokine receptors are overexpressed?

A

They can cause tumor cells and are being looked at therapeutically to help suppress this

40
Q

What are the cytokine receptors?

A
  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
Q

How many chemokines are in the human family and how many receptors

A

There are 46 protein chemokines and 23 GPCR receptors

42
Q

Cytokine receptors

A

They have cross-reactivity so they can have different cytokines bind to the same receptor

43
Q

Type 1 cytokine receptor intracellular domain (spider)

A

A huge complex inside of the cell with up to 600 residues, they are very atypical

44
Q

how to terminate a signal

A

rapid reducing the message by use of SERT
breakdown of enzymes by acetylcholine esterase
less signal over time but with the same concentration

45
Q

RTKs

A

receptor tyrosine kinases that leads to phosphorylation of downwards signaling

46
Q

What activates Ras/MAP kinase?

A

RTK receptor tyrosine kinases

47
Q

When Ras is activated what does it do?

A

Activates cell proliferation, migration, transformation, survival but mutations can lead to cancer

48
Q

What are the three Ras genes?

A

HRas, Kras, Nras

49
Q

what are cytokines?

A

small proteins used to control growth and immune system cells to execute inflammation responeses

50
Q

pleiotropic…..

A

the same cytokine can bind to different receptors and have a different effect

51
Q

redundant

A

when different cytokines produce a similar effect

52
Q

cascade effect

A

cytokines can stimulate the production of other cytokines

53
Q

TNF-a

A

tumor necrosis factor that gets released upon infection from macrophages

54
Q

Chemokines do what?

A

cell migration and theyre also called CXCL8

55
Q

What is Icam and LFA-a

A

Where leukocytes go through rolling adhesion and stop because of the extracellular receptor Icam

56
Q

Siltuximab

A

cancer drug which inhibits IL-6

57
Q

Tocilizumab and Sarilumab

A

cancer drugs which inhibits IL-6 receptor

58
Q

Adaptive immunity

A

Remember and specific respond slower (B and T-cells)

59
Q

Innate immunity

A

respond much faster non-specific and have no memory

60
Q

What are the ways that GPCRs terminates signaling

A

Phosphorylation of G-protein coupled receptor
b-arrestin
internalization in clathrin-coated pit
recycling or degradation

61
Q

Gproteins and who they effect in GPCRs

A

Gs and Gi both effect adenylyl cyclase -> cAMP -> PKA
Gq effects phospholipase C - Diacylglycerol OR IP3 -> PKC OR IP3 receptor -> CALCIUM

62
Q

CaM or calmodulin does what?

A

A small protein that binds to excess calcium and releases it

63
Q

ori?

A

Origin of replication

64
Q

What is topoisomerase do?

A

Essential for termination

65
Q

What is p53?

A

A tumor suppressant protein

66
Q

What do methotrexate and 5-flurouracil do?

A

They inhibit DNA replication to make sure the tumor cant keep growing

67
Q

BCR-ABL what is it?

A

Causes cancer and shorten chromosome length

68
Q

What is chromatin?

A

a long chain of wound up dna histones

69
Q

epigenetics

A

post-transloational modifications of histones

70
Q

What do HATs do?

A

They open up dna on a histone (acetylation)

71
Q

What do HDACs do?

A

They wind the dna back up on the histone (deacetylation)

72
Q

Transcription

A

Makes mRNA

73
Q

Translation

A

mRNA goes through a ribosome and adds codons

74
Q

Chaparone

A

Helps fold DNA

75
Q

Misfolded proteins are called what?

A

Aggregation

76
Q

Posttranslational modifications (PTMs) do what?

A

They add complexity to the proteome

77
Q

What do large aggregates cause?

A

Can cause alzheimers, parkinsons, or hunningtons

78
Q

Ubiquititin-proteasome proteolysis

A

A process that is targeted for degredation as part of cellular function

79
Q

Lysosomal degredation

A

membrane-bound organelles containing proteases that can degredate exogenous proteins or aged/damaged organelles

80
Q

Autophagy

A

Self engulfing process that gets rid of trash / defective organelles

81
Q

Defective autophagy casues

A

alzheimers

82
Q

Targets protein degredation by the proteasome, whats it made of

A

2x 19s complex and 1x 20s core complex

83
Q

Ubiquitin-proteqsomal system process

A

E1 (activating), E2 (conjugating), E3 (ligase),need at least 4 ubiquitin molecules to be able to degrade

84
Q

What activity does the 20s proteasome have?

A

Trypsin, caspase and chymotrypsin

85
Q

Oxidative stress and proteasome

A

disassembles the 19s complex and leaves the 20s complex to degrade oxidized proteins

86
Q

degron

A

recognition sequence or structure for an E3 ligase

87
Q

Bortezomib

A

A cancer drug, the first proteasome inhibitor

PHRM836 (2 decks)

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