Cell signaling Flashcards

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1
Q

Cells use chemicals to

A

communicate

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2
Q

a signaling cell produces and releases a

A

signal molecule

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3
Q

A target cell receives the signal using a

A

protein receptor that binds the signal

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4
Q

The receptor transmits a signal to begin an

A

intracellular signaling cascade

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5
Q

The cell responds through what type of change

A

physiological

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6
Q

Signal transduction is how cells do what

A

Communicate

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7
Q

1st type of extracellular signaling type

A

Autocrine

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8
Q

2nd type of extracellular signaling type

A

Paracrine

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9
Q

3rd type of extracellular signaling type

A

Contact-dependent

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10
Q

what is autocrine

A

= self-signaling
* Note on your fridge you write to
remind yourself of the party you are
throwing

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11
Q

what is paracrine

A

= short-distance or localized
* Invitations you place in your
coworkers’ mailbox at work or under
the front door of some nearby friends’
houses

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12
Q

what is contact dependent

A

= surface-to-surface contact
* Invitation you physically hand to your
next-door neighbors

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13
Q

4th type of extracellular signaling type

A

Endocrine

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14
Q

5th type of extracellular signaling type

A

Neuronal

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15
Q

6th type of extracellular signaling type

A

Neuroendocrine

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16
Q

What is endocrine

A

= long-distance, hormonal (uses circulation)
* Mailing out invitations to some of your
friends and family that live far away

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17
Q

What is neuronal

A

= synaptic neurotransmitters
* Sending a text to someone who lives far
away (since you don’t have their address)

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18
Q

What is neuroendocrine

A

= long-distance, where synaptic neurotransmitters instead secrete into circulation
* Mailing out invitations via email or similar
social media accounts for your friends and
family whose addresses/phone numbers
you don’t have (starts electronically, but
wide dispersal like mail)

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19
Q

Receptor Proteins can be what

A

Can be transmembrane receptor
proteins…
* For signals that are either too big,
polar, or charged to enter the cell
* …or intracellular receptor
proteins
* For signals that can cross the cell
membrane (gases, steroids, etc.)

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20
Q

Receptors are highly specific for
a signaling molecule their what

A

ligand

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21
Q

Since receptors are highly specific, what does that mean?

A

This means that most receptors are
only stimulated by a certain molecule
* Some exceptions = “maskable”
scents for similar chem. structures

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22
Q

Cells respond to signals in different ways based upon

A

differentiation

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23
Q

Not all cells will express the same subset of

A

receptors

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24
Q

So, while a signal could reach every cell in the body, only select cells WITH THE RIGHT RECEPTOR will recognize/respond to it. What are the exceptions?

A

Exceptions = receptors needed for MOST cells, just in case, like
immune-related receptors which communicate they are infected

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25
Q

Multiple signals in different combinations result in different cellular

A

outcomes

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26
Q

Allows for subtle and complex control

A

activities

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27
Q

Intracellular relay systems are important for causing

A

outcomes

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28
Q

Response Can Be Fast or Slow
Fast:

A

activity of an existing protein is modified

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29
Q

Response Can Be Fast or Slow
Slow:

A

new gene expression occurs and takes longer before a protein is made

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30
Q

Surface receptors bind
their

A

ligand

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31
Q

The receptor activates

A

intracellular signaling molecules

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32
Q

Signaling events lead to various

A

potential cellular changes

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33
Q

There are multiple effects depending on the molecules involved in intracellular signaling pathways, what are they?

A

Relay the signal onward and may spread it throughout the cell
* Amplify the signal to make it stronger
* Detect signals from more other receptors to integrate signals
* Distribute the signal to lead to more than one outcome
* Modify the signal based on feedback, positive or negative (usually negative)

34
Q

Intracellular Molecular Switches kinases and phosphatases cause what

A

covalent modification of signaling proteins (stimulatory or inhibitory)

35
Q

GTP-binding proteins (G proteins)

A

Active/inactive depending on
GTP/GDP binding
* GAPs turn them “OFF” while GEFs turn
them “ON”…especially if MONOMERIC

36
Q

What are the three types of surface receptors

A

Ion-channel-coupled receptors, G-protein-coupled receptors (GPCRs), Enzyme-coupled receptors

37
Q

What are Ion-channel-coupled receptors

A

change permeability of the membrane to select ions, altering membrane potential (e.g., Na+ channels)

38
Q

What are G-protein-coupled receptors (GPCRs)

A

Activate trimeric GTP-binding proteins, which then activate or inhibit other signaling proteins and second messengers
ocAMP, Ca2+, IP3, DAG, cGMP, NO, and PKA / PKC kinases

39
Q

what are Enzyme-coupled receptors

A

Are enzymes or associate with enzymes to activate a cascade
Often trigger monomeric GTP-binding proteins of the Ras superfamily

40
Q

Signaling across synapses using neurotransmitters, including

A

neuromuscular junctions

41
Q

Ion Channel-Coupled
Receptors

A

Action potential triggers VG-Ca2+ channels
o Ca2+ triggers exocytosis
o Synaptic vesicles dump acetylcholine into the synaptic cleft
Acetylcholine binds an
ion-channel coupled
receptor, which allows
sodium to enter the cell
o An action potential
propagates along the
skeletal muscle cell
o Transverse tubules bring
voltage to ER-VG-Ca2+

42
Q

G-Protein Coupled Receptors

A

There are different ligands for different types of GPCRs
* Exception = smell masking…more likely in humans than mice
* All have 7 transmembrane domains
* All of them can interact with trimeric G-proteins (αβγ)
* Alpha will self inactivate w/GTPase hydrolytic activity, no GAP necessarily required

43
Q

When bound by their ligand,
GPCRs undergo a conformational
change to interact with

A

(trimeric) G proteins

44
Q

When G proteins bind to their ligand what takes place

A

Causes release of GDP from the
alpha G protein subunit
* GTP binds alpha (GEF not
necessarily required), activating the
G protein
* α and βγ subunits may or may not
dissociate, but either way, will
activate a target molecule

45
Q

GPCRs activate enzymes that
increase

A

intracellular signaling
molecule concentrations

46
Q

intracellular signaling
molecule concentrations called what

A

second messengers

47
Q

After a delay, GTP is hydrolyzed
to GDP, deactivating what

A

The G protein

48
Q

After the delay and GTP is hydrolyzed to GDP what are two things that happen

A

α and βγ re-associate (inactive)
* New ligand-GPCR interactions
reinitiate the signaling cascade

49
Q

Adenylyl cyclase produces

A

cyclic AMP (cAMP)

50
Q

Adenylyl cyclase produces cyclic AMP (cAMP) and leads to what

A

Extensive effects in both prokaryotes & eukaryotes
* Epinephrine signals through cAMP in heart cells to quickly contract, and in fat/skeletal muscle cells (below)
* Adenylyl cyclase is a target of caffeine (prolongs cAMP)

51
Q

cAMP signals via protein kinase A (PKA) has two types of events

A

Fast event = glycogen breakdown
* Slow event = altered gene expression

52
Q

Acetylcholine signals through GPCR and does what

A

Triggers IP3, then Ca2+
(more next slide)
* Generates
Nitric Oxide (NO)
* Through cyclic GMP (cGMP), the NO signal causes vasodilation
* How nitroglycerin (NO stim.) & Viagra (cGMP inh.) work

53
Q

Phospholipase C (PLC) phosphorylates & cleaves a membrane phospholipid (phosphatidylinositol-phosphate-2, or PIP2) and produces what

A

Produces inositol-triphosphate (IP3) and diacylglycerol (DAG)

54
Q

IP3 triggers the second messenger Ca2+ release and what are examples of what could happen

A

Egg development upon fertilization
* Muscle contraction
* Cell secretion

55
Q

DAG activates Protein Kinase C (PKC) and what happens

A
  • Smooth muscle contraction (vasoconstriction, bronchoconstriction)
  • Parasympathetic related secretions (gastric enzymes, saliva, etc.)
  • Immune signaling (CARD-CC proteins)
56
Q

Enzyme-Coupled Receptors

A

Ligands bind the external portion of a transmembrane receptor

57
Q

Cytoplasmic portion activates or interacts with an

A

internal membrane protein that activates a signaling cascade

58
Q

Signals generally slower and require multiple

A

transduction steps

59
Q

Largest class of enzyme coupled receptors is

A

Largest class of this type is RTKs (receptor tyrosine kinases)

60
Q

RTKs are usually dimers, but the two subunits are separated w/o ligands, what is an example?

A

Epidermal Growth Factor Receptor (EGFR)

61
Q

Upon ligand binding & subsequent dimerization, auto-phosphorylation of the dimer occurs, recruiting the next

A

signaling proteins at the membrane

62
Q

Many RTKs act through Ras, what is Ras?

A

a small GTP-binding protein attached to the cytosolic face of the membrane

63
Q

While the previous G proteins were trimeric (α, β, γ), Ras is considered what

A

Monomeric (monomeric G-proteins usually aren’t coupled to GPCRs)

64
Q

Activated RTK signaling activates a Ras-GEF, which causes Ras to release what?

A

GDP and bind GTP (activating Ras!!!)

65
Q

Ras activates what

A

intracellular signaling molecules and leads to protein activity and gene expression

66
Q

What does MAPK stand for

A

mitogen-activated protein kinase

67
Q

What is Mitogen

A

something that generates mitosis, a.k.a. the cell cycle ex: growth factor

68
Q

MAPK’s can form a series what is it

A

A kinase may phosphorylate another kinase…and so on…
* MAP3K→MAP2K→MAPK
* Raf→MEK→ERK

69
Q

RTKs also promotes cell growth & survival through

A

AKT

70
Q

PI3-kinase is activated by an RTK, which phosphorylates

A

the inositol phospholipid to produce PIP3

71
Q

PIP3 (formed from phosphorylation of PIP2) attracts what

A

phospholipase D kinase 1 (PDK1) and Akt; former activates latter

72
Q

Akt activates what

A

mTOR, Bcl2, survivin, and inhibits Bad & (indirectly) inhibits p53
…blocking programmed cell death = inhibits apoptosis)
* mTORs = mammalian
target of rapamycin (Promotes translation)
Inhibits protein degradation
mTOR = cell growth
signaling protein

73
Q

mTORs

A

mammalian target of rapamycin (Promotes translation)

74
Q

mTOR

A

cell growth signaling protein

75
Q

What is Apoptosis

A

programmed cell dealth

76
Q

What happens in Apoptosis

A

Nucleases condense and
cleave chromatin, Organelles break down, Cell debris packaged into apoptotic bodies, avoids tissue-damaging inflammation

77
Q

What is AKT and Bcl-2’s role is apoptosis

A

They are are pro-survival proteins which block apoptosis

78
Q

Bcl-2 homology-domain containing proteins (like Bad) associated with mitochondria can have pro-apoptotic effects;

A

Can be activated internally/intrinsically (like via p53 signaling)…
* …Or externally/extrinsically (like via contact with a cytotoxic T cell)

79
Q

(pro)Caspases are often inactive in all cells, what does this mean?

A

ny cell could trigger rapid apoptosis, during events like
o Upon infection
o To regulate cell numbers
o To form correct organ shapes

80
Q

Triggering mitochondrial leakiness leads to

A

Cytochrome C release, Activates more caspases (other pathways possible), and is the Point of no-return!

81
Q

GPCRs and RTKs are involved in many important signaling events in a cell, disruption of these can

A

have significant impacts