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Cell Bio > Principles of Cell Signaling > Flashcards

Principles of Cell Signaling Flashcards

1
Q

what do signaling cells produce

A

an extracellular signal molecule which is detected by a target cell

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2
Q

what do target cells do in cell signal transduction

A
  • recognize and respond to extracellular signal molecules via receptors that are specific to signal molecules
  • target cell converts the extracellular signal to an intracellular signaling molecule to alter cell behaviour
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3
Q

what are the 4 methods of cell signal transduction

A
  • endocrine signal transmitted throughout entire system via bloodstream
  • paracrine signals transmitted locally in extracellular fluid
  • neuronal signal transmitted to a specific target
  • contact-dependent signal transmitted to cells in direct contact
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4
Q

what is autocrine signaling

A

cells responding to local mediators that they produce themselves

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5
Q

where are large hydrophilic signals recognized

A

plasma membrane

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6
Q

where are small hydrophobic signals recognized

A

cytosol

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7
Q

signal reception is limited and controlled how

A

through the expression of receptors

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8
Q

do cells depend on extracellular signals

A

yes, multiple

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9
Q

absence or inhibition of appropriate signals leads to what

A

cell death (apoptosis)

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10
Q

can signals modify effects of each other

A

yes (allows them to finely tune the cells response)

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11
Q

can extracellular signals elicit responses at diff speeds

A

yes

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12
Q

what speeds can extracellular signals elicit responses at

A
  • fast response change in protein activity already present in the cell
  • slow response change in gene expression and protein synthesis
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13
Q

where are most extracellular signal molecules recognized

A

plasma membrane

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14
Q

how is a response to an extracellular signal recognized at the plasma membrane generated

A

the activation of an effector protein

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15
Q

what functions to intracellular signaling pathways perform

A
  • relay aid in spread through the cell
  • amplify make the signal stronger
  • integrate limit relay until there are multiple signals
  • distribute relay signals to multiple effectors
  • engage in feedback alter response by regulating components upstream in signaling pathway
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16
Q

what are the two kinds of feedback

A
  • positive downstream components enhances initial signal (all or nothing)
  • negative downstream components inhibits initial signal (oscillating)
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17
Q

where can feedback occur

A

anywhere in the signaling pathway

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18
Q

what does it mean for a protein to behave as molecular switches

A

once they receive a signal they switch to an active or inactive state

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19
Q

what are two kinds of protein switches

A
  • phosphorylation phosphate group is bound or cleaved, changing activation
  • GTP-binding active when bound to GTP and inactive when bound to GDP
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20
Q

what do kinases do

A

transfer a phosphate group to a molecule

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21
Q

what do protein kinases do

A

transfer terminal phosphate from ATP to a serine, theronine, or tyrosine side chain

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22
Q

what are the 2 main types of GTP-binding proteins

A
  • monomeric GTPases controlled by regulatory proteins (GEF and GAP)
  • G proteins large, trimeric, relay messages from G-protein coupled receptors
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23
Q

what does GEF stand for

A

guanine nucleotide exchange factor (a regulatory protein for monomeric GTPases)

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24
Q

what does GAP stand for

A

GTPase-activating protein (a regulatory protein for monomeric GTPases)

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25
Q

what do cell-surface receptors do

A

bind to an extracellular signals and transduce its message into one or more intracellular signaling molecules

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26
Q

what are the primary classes of cell-surface receptors

A
  • ion-channel-coupled
  • G-protein-coupled
  • enzyme-coupled
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27
Q

how many receptors are there for extracellular signaling molecules

A

more than one type

28
Q

what do ion-channel-coupled receptors do

A
  • change the permeability of the plasma membrane to selected ions
  • alter membrane potential
  • sometimes produce an action potential
29
Q

what do G-protein-coupled receptors do

A
  • activate membrane-bound GTP-binding proteins
  • activate or inhibit an enzyme/ ion channel in the plasma membrane to trigger an intracellular signaling cascade
30
Q

what do enzyme-coupled receptors do

A
  • act an enzymes or associate w enzymes inside the cell
  • activate a wide variety of intracellular signaling pathways
31
Q

what are the largest family of surface receptors

A

G-protein-coupled receptors (GPCRs)

32
Q

describe the structure of GPCRs

A

single polypeptide chain that traverses the plasma membrane 7 times

33
Q

what GPCRs do

A
  • involved in many cell processes
  • mediate responses to a diverse range of extracellular signals
34
Q

describe the structure of G proteins

A
  • composed of 3 protein subunits: alpha, beta, gamma
  • alpha and gamma subunits are tethered to membrane via covalently linked lipids
35
Q

what happens when an extracellular signal binds to a GPCR

A
  • receptor activates a G protein on the cytosolic side of the membrane
  • this alters the affinity of the alpha subunit for GDP
  • GDP is exchanged for GTP
  • this may separate the G protein into 2 activated parts: alpha subunit, beta/gamma subunit
  • the effector is now activated!!!
  • eventually alpha subunit will hydrolyze bound GTP to GDP
  • G protein now returns in inactive conformation
36
Q

active time of the G protein components is determined by what

A

the behaviour of the alpha subunit

37
Q

how can the bound GTP being hydrolyzed tto GDP be accelerated

A

by a regulator of G-protein signaling (RGS) protein

38
Q

G proteins directly regulate the activity of what

A

ion channels

39
Q

how do G proteins slow heart rate

A
  • nerve signals to slow heart rate release acetylcholine
  • acetylcholine bind to GPCR
  • this activates the G protein
  • the beta/gamma complex binds to the intracellular face of a K+ channel, forcing it open
40
Q

what does adenylyl cyclase do

A

produces cyclic AMP

41
Q

what does phospholipase C do

A

produces inositol triphosphate and diacylglycerol

42
Q

what are 2 most frequent taregts when activating membrane-bound enzymes

A
  • adenylyl cyclase
  • phospholipase C
43
Q

how does the cyclic AMP pathway work

A
  • activated G protein alpha subunit switches on adenylyl cyclase
  • this increases the synthesis of cAMP from ATP
  • cyclic AMP phosphodiesterase coverts cAMP into AMP, terminating the signal
  • cyclic AMP phosphodiesterase is always active inside the cell to make this signal termination quick
44
Q

how does cAMP exert most of its effects

A
  • by activating cyclic-AMP-dependent protein kinase (PKA)
  • this phosphorylates specific target proteins which vary depending on cell type
45
Q

what kinase is active in cAMP signaling- enzyme activation

A

PKA

46
Q

what kinase is active in cAMP signaling- gene transcription

A

PKA

47
Q

what kinase is active in the inositol phospholipid pathway

A
  • inositol 1.4.5-triphosphate (IP3)
  • diacylglycerol (DAG)
48
Q

what is the largest class of enzyme-coupled receptors

A

receptor tyrosisne kinases (RTKs)

49
Q

how do receptor tyrosisne kinases (RTKs) work

A

cytosolic domain phosphorylates tyrosines on intracellular signaling proteins

50
Q

what are enzyme coupled receptors

A

receptors that form a complex w another protein, which acts an enzyme or the cytosolic domain of the receptor itself acts as an enzyme

51
Q

in many cases, binding of an extracellular signal causes two receptors to form a _____, which does what

A
  • dimer
  • where each receptor tail phosphorylates the other activating the kinase domains
52
Q

what happens in active RTKs

A

the newly phosphorylated tyrosines serve as docking sites for intracellular signaling proteins

53
Q

what are some of the roles of intracellular signaling proteins that dock on active RTKS

A
  • some only as scaffolds
  • others are activated upon binding to aid in the propogation of the signal
54
Q

how long are RTK signal complexes active for

A

until it is dissociated by tyorsine phosphatases or the complex is degraded via endocytosis

55
Q

RTKs recruit and activate what

A
  • many kinds of intracellular signaling proteins
  • including the monomeric GTPase Ras
56
Q

what is Ras

A
  • resembles and functions in a similar manner to the alpha subunits in trimeric G proteins
  • activate when bound to GTP
  • inactive when bound to GDP
57
Q

describe Ras in its active state

A
  • when bound to GTP
  • it initiates phosphorylation cascades to transmit a signal from the plasma membrane to the nucleus
58
Q

describe RTK-mediated signal transmission from the plasma membrane to the nucleus

A
  • includes a 3-kinase module named MAP-kinase signaling module
  • this is named after the final enzyme in the sequence (MAP- kinase)
59
Q

what does MAP kinase do

A
  • phosphorylates various proteins including transcription regulators
  • may stimulate proliferation, survival, or induce differentiation
60
Q

RTKs can promote cell growth how

A

by activating phosphoinositide 4-kinase (PI 3-kinase)

61
Q

what do PI 3-kinase do

A

phosphorylated inositol phospholipids in the plasma membrane to serve as docking sites for intracellular signaling proteins (including Akt)

62
Q

what kinases are present in PI-3-Kinase-Akt signaling pathway

A
  • PI 3-kinase
  • Akt (aka PKB)
63
Q

what does Akt do

A
  • promotes survival often through the inhibition of signaling proteins
  • promotes cell growth through the activation of signaling proteins
64
Q

how does Akt promote survival

A

phosphorylates and inactivates the cytosolic signaling protein Bas, which activates apoptosis

65
Q

how does Akt promote cell growth

A

indirectly activates a large serine/threonin kinase, Tor, that stimulates protein synthesis and inhibits protein degredation

66
Q

what allows for finely tunes responses to a combination of signals

A

integrating the information from a high volume of messages for an appropriate response

67
Q
A

Cell Bio (11 decks)

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