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BMSC 220 > Topic 11 > Flashcards

Topic 11 Flashcards

1
Q

4 steps to cell signalling

A
  • signalling molecules released (ligands)
  • recognition of signalling molecule by target cell (receptors)
  • signal transduction; signalling cascade (conversion of extracellular signal into intracellular instructions)
  • final impact on target cell and subsequent impact on organism as whole
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2
Q

Cell communication and signal transduction __________ in complexity with multicellular organisms

A

increases

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3
Q

modes of signalling

A
  • cell to cell
  • paracrine (neurotransmitters across a synapse)
  • endocrine (hormones)
  • autocrine
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4
Q

5 classes of ligands

A
  • steroid hormones
  • eicosanoids
  • neurotransmitters
  • peptide hormones and polypeptide growth factors
  • simple gases
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5
Q

steroid hormones

A
  • hydrophobic molecules that can diffuse across cell membrane and bind to intracellular receptors
  • estrogen, glucocorticoids
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6
Q

steroid hormones mode of action

A

endocrine, paracrine, and autocrine

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7
Q

eicosanoids

A

-hydrophobic, rapidly broken down that bind to cell surface receptors

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8
Q

eicosanoids mode of action

A

paracrine or autocrine

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9
Q

neurotransmitters

A

-hydrophilic and bind to cell surface receptors

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10
Q

neurotransmitters mode of action

A

endocrine, paracrine, and autocrine

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11
Q

peptide hormones and polypeptide growth factors

A
  • largest and most variable, primarily hydrophilic and cannot cross cell membrane but bind to cell surface receptors
  • insulin, epidermal growth factor
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12
Q

peptide hormones and polypeptide growth factors mode of action

A

endocrine, paracrine, and autocrine

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13
Q

simple gases

A

-passive diffuse across membrane, bind directly to enzymes and do not use receptors

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14
Q

simple gases mode of action

A

paracrine

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15
Q

two classes of receptors

A

intracellular and cell surface

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16
Q

nuclear receptor superfamily

A

intracellular receptors that primarily function as transcription factors
-glucocorticoids, thyroid hormone

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17
Q

3 types of cell surface receptors

A
  • g-protein coupled receptors (integral membrane protein)
  • receptor protein tyrosine kinases (integral membrane protein)
  • cytokine receptor superfamily (peripheral membrane protein)
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18
Q

cytokine receptor superfamily function together with..

A

non receptor protein tyrosine kinases

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19
Q

glucocorticoid action

A
  • inactive when bound to a chaperone

- become active when bound to the ligand

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20
Q

dimer

A

two active receptors that translocate to nucleus and associate with co-activator protein HAT

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21
Q

active gene transcription

A

glucocorticoid receptor + ligand + HAT coactivator

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22
Q

gene regulation by thyroid hormone receptor

A
  • receptor (dimer) bound to DNA with or w/o ligand
  • w/o ligand receptor binds corepressor HDAC to repress gene transcription
  • hormone binds receptor changing conformation to disassociate from HDAC and associate with coactivator HAT allowing gene transcription
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23
Q

g-protein coupled receptors

A

largest family of cell surface receptors and are transmembrane proteins with multiple transmembrane domains

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24
Q

g-protein

A

transmits G protein coupled receptor signals to intracellular targets via intermediary protein

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25
Q

When extracellular receptor domain binds the ligand of g-protein coupled receptors

A

causes a conformational change activating a G protein. alpha subunit of G protein dissociates from beta and gamma to carry signal to intracellular target

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26
Q

adenylyl cyclase

A

intracellular target molecule

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27
Q

tyrosine kinase receptors

A
  • plinked ot intracellular enzymes
  • one transmembrane domain
  • enzyme activity by intracellular domain of receptor or separate protein associated with intracellular domain
28
Q

how are tyrosine kinase receptors activated

A

by phosphorylating tyrosine residues on both receptor and target substrates which can then associate with downstream targets and initiate a signalling cascade

29
Q

What proteins can recognize tyrosine kinase receptors?

A

-insulin and multiple growth factors

30
Q

how do tyrosine kinase receptors change when activated?

A

dimerization followed by phosphorylation

31
Q

non receptor tyrosine kinase

A

associate with receptors that contain no catalytic activity

32
Q

intracellular signal transduction

A

chain of reaction that transmit chemical signals from cell surface to their intracellular targets (signalling cascade)

33
Q

4 pathways of intracellular signal transduction

A
  • 2 indirectly connected ti transcription factors (cAMP and MAP kinase)
  • 2 directly coupled to transcription factors (Notch signalling and Wnt pathway)
34
Q

cAMP

A

cyclic AMP is an important second messenger associated with G protein coupled receptors and is important for response of cells to variety of hormones

35
Q

A phosphate group in cAMP is covalently bound to both the 3’ and 5’ carbon atoms by the enzyme….

A

adenylyl cyclase

36
Q

second messenger

A

a compound that is modified as a result of ligand-receptor interaction and relays message from receptor to target
-can be used in multiple pathways

37
Q

adenylyl cyclase

A

an enzyme that catalyzes formation of cAMP from ATP; stimulated by alpha subunit of activated G protein

38
Q

cAMP phosphodiesterase

A

an enzyme that degrades cyclic AMP

39
Q

The second messenger _____ initiates intracellular transduction

A

cAMP

40
Q

regulation of protein kinase A

A

cAMP binds to cAMP dependent protein kinase called protein kinase A (PKA) causing dissociation of PKA regulatory subunits and it phosphorylates downstream target proteins

41
Q

PKA and CREB

A

PKA activates transcription factor CREB by phosphorylation; CREB recruits coactivators and initiates transcription at CRE binding sites

42
Q

CRE

A

specific DNA binding element that is in the promoter region of cAMP responsive genes

43
Q

PKA and glycogen

A

In regulation of glycogen metabolism, PKA phosphorylates two target enzymes; activates phosphorylase kinase and inhibits glycogen synthase

44
Q

cAMP signaling pathways can effect both…

A

transcription factors and metabolic enzymes

45
Q

PP1- protein phosphatase 1

A

counterbalances PKA activity to fine tune the signalling mechanism

46
Q

A single receptor can activate_______ G proteins

A

multiple

47
Q

1 hormone molecule binding 1 receptor can activate ____ target proteins.

A

many

48
Q

MAP (mitogen activated protein) kinase

A

cell surface receptors linked to enzymes to produce intracellular signals

49
Q

MAP kinase pathways can be associated with…

A

both receptor and nn receptor tyrosine kinases

50
Q

MAP kinases are activated in response to…

A

a variety of growth factors and other signalling molecules

51
Q

stereotypical MAP kinase pathway

A

Ras-Raf-MEK-ERK

52
Q

Raf

A

rapidly accelerating fibrosarcoma; a protein serine/threonine kinase that is activated by Ras and leads to activation of ERK MAP kinase

53
Q

ERK

A

extracellular signal-regulated kinase

54
Q

MEK

A

map kinase/ERK kinase; dual specificity protein kinase that activates members of ERK family by phosphorylation of both threonine and tyrosine residues

55
Q

Ras

A

rat sarcoma; guanine nucleotide-binding proteins that function analogously to alpha subunits of G proteins alternating between inactive GDP-bound and active GTP bound forms; integral membrane lipoprotein

56
Q

___ could be directly linked to growth factor induced cell proliferation

A

Ras

57
Q

one of the first oncogenes identified in human cancers

A

Ras

58
Q

GEF

A

guanine exchange factor; activates Gas

59
Q

mutated Ras

A

locked in GTP binding form

60
Q

GAP

A

guanine activating protein; terminates Ras activity

61
Q

intermediate protein

A

links phosphorylated region of tyrosine kinase with other target molecules

62
Q

notch signalling

A

example of cell to cell signalling;

  • notch receptor receives signal from delta ligand on surface of an adjacent cell
  • this activates gamma-secretase enzyme to cleave intracellular domain of notch
  • domain translocates to nucleus where it binds and activates transcription factors
63
Q

intracellular domain

A

vehicle for signal transduction

64
Q

Wnt pathway

A

Wnt proteins (ligand) is family of secreted growth factors involved in cell fate pathways

  • bind to receptors Frizzled and LRP
  • Wnt, Frizzled andLRP recruit Dishevelled disrupting the destruction complex of proteins
  • this prevents phosphorylation go transcription factor B-Catenin
  • once unphosphorylated, is stabilized and can translocate to nucleus
  • bind to a repressor and form a complex to activate gene transcription
65
Q

crosstalk

A

interaction of one signalling pathway with another

66
Q

final impact on cell/organism depends on..

A

signal pathways intersecting/ crosstalk

BMSC 220 (12 decks)

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