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MBB 231 > Lecture 23 - Cell Signalling & Transmission III > Flashcards

Lecture 23 - Cell Signalling & Transmission III Flashcards

1
Q

____ signalling pathways often regulate differentiation, cell division, and survival

A

RTK

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2
Q

def: signals/messengers that stimulate cell growth in dividing cells

A

growth factors

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3
Q

what does extracellular ligands binding result in?

A

dimerization of the receptors

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4
Q

what do the ligand-bound receptors do to the cytoplasmic domains of the receptors?

A

trans-auto-phosphorylate the cytoplasmic domains of the receptors

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5
Q

how are cytoplasmic signalling molecules activated?

A

by binding to phosphorylated tyrosine on the active receptor

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6
Q

cytoplasmic signalling molecules associated with the receptors through ______ and ______ domains

A

SH2 and PTB

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7
Q

def: ~100 amino acids long and contain a conserved binding pocket that interacts with pTyr

A

SH2 domains

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8
Q

what determines the specificity of different SH2 domains?

A

the amino acids surrounding the phosphorylated tyrosines

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9
Q

what does the extracellular domain of a pTyr do?

A

binds ligand

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10
Q

what does the single transmembrane helix of a pTyr do?

A

participates in dimerization

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11
Q

what does the dimerization/aggregation of a pTyr do?

A

activates the RTK(generally)

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12
Q

what does the large cytosolic domain of a pTyr do?

A

location of the kinase, phosphorylation target sites, and SH2 binding site

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13
Q

def: act as linkers enabling two or more proteins to form a signalling complex

A

adaptor/scaffolding proteins

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14
Q

what is a Grb2 an example of?

A

an adaptor protein

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15
Q

the SH2 domain of Grb2 binds to RTKs, while the SH3 domain is constitutively associated with _____

A

Sos

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16
Q

The PTB domain of IRS binds to ______s, leading to the phosphorylation of IRS tyrosines

A

RTK

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17
Q

the SH2 domain of STAT binds to ____, which phosphorylates tyrosine in ______. this allows STAT to dimerize, forrming a _________ _________ ___________ that translocated to the nucleus and activate gene expression

A

RTK, STAT, functional transcription factors

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18
Q

signalling enzymes, equipped with SH2 domains, can directly associate with RTKs, these can include:

A
  • protein kinases
    -protein phosphatases
  • lipid kinases
    phospholipases
    GTPase activating proteins
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19
Q

what are the 3 ways activation occur in protein pTyr and signal transduction?

A
  1. recruitment of the enzymes to the membrane, placing them in close proximity to their targets
  2. binding of the pTyr can result in conformational changes ini the catalytic domain increasing/decreasing the catalytic activity
  3. phosphorylation of the enzyme to increase or decrease the catalytic activity
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20
Q

how does termination of TRK signalling occur?

A

through internalization of the receptors, essentially the same pathway as GPCRs termination

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21
Q

T or F: RTK’s do not require Arrestin

A

True, they have a short motif in their cytoplasmic domain that can interact with AP2

22
Q

in RTK termination, what are the 3 possible outcomes?

A
  1. receptor signalling can resume within the endosome
  2. the receptor can be trafficked to the lysosome for degradation
  3. the receptor can be returned to the cell surface
23
Q

def: if a receptor returns to the cell surface, they can resume signalling

A

re-sensitization

24
Q

Ras is a ____________ G protein

A

signal transduction

25
Q

Ran is a ____________ G protein

A

nuclear transport

26
Q

Rab is a ____________ G protein

A

tethering vesicles

27
Q

Sar1 is a ____________ G protein

A

vesicle formation

28
Q

Rho is a ____________ G protein

A

actin-binding protein regulator

29
Q

what does GAPs stand for?

A

GTPase activating proteins

30
Q

what does GDIs stand for?

A

guanine nucleotide dissociation inhibitors

31
Q

what does GEFs stand for?

A

guanine nucleotide exchange factors

32
Q

how is the Ras-MAP pathway activated?

A

when a growth factor binds the extracellular domain of an RTK

33
Q

what are the 4 main steps after ligand binding in Ras-MAP?

A
  1. dimerization of two receptors
  2. trans-autophosphorylation of cytosolic portion of the RTK protein
  3. SH2 domain containing protein Grb2 has high affinity for the pTyr on the RTK
  4. Grb2 is constitutively associated with a RasGEF called Sos
34
Q

what does recruitment of Sos to the membrane do?

A

brings the RasGEF into close proximity with Ras, allowing GDP to be replaced with GTP = ACTIVATION OF RAS

35
Q

what does Ras-GTP have a high affinity for?

A

protein kinase Raf

36
Q

what does Raf phosphorylate?

A

serine and threonine residues in a protein kinase called MEK

37
Q

what does MEK phosphorylate?

A

ERK or mitogen activated protein kinase (MAPK)

38
Q

growth factor binding leads to….

A

cell proliferation

39
Q

T or F: once Ras is in the active state, it must be inactivated to avoid continual stimulation of the Ras pathway

A

true

40
Q

what deactivates the Ras pathway?

A

GTPase activating protein (RasGAP) that facilitates GTP hydrolysis

41
Q

Ras mutations are common in _________

A

cancer

42
Q

scaffolding proteins can tether different MAP kinase pathways together, ________ ____________ __________ ____________-

A

physically linking signalling pathways

43
Q

def: activation of a common effector/2nd messenger

A

convergence

44
Q

def: one RTK can activate 3 different pathways

A

divergence

45
Q

steroids are ________ proteins?

A

soluble proteins

46
Q

what are the 2 domains of a nuclear receptor?

A
  1. ligand binding domain
  2. DNA binding domain
47
Q

what are 3 properties of the DNA binding domain of nuclear receptors?

A
  1. steroid receptors act by binding specific DNA enhancer sequences called hormone receptor elements (HRE)
  2. the DNA binding domain is usually two Zinc-Finger motifs
  3. binding to the HRE leads to either enhanced or repressed gene expression
48
Q

what is the starting material for synthesis of steroid hormones?

A

cholesterol

49
Q

def: family of hormones that promote synthesis of glucose and suppress inflammation

A

glucocortoids

50
Q

def: regulate ion balance by promoting reabsorption of sodium, chloride, and bicarbonate ions by the kidney

A

mineralcorticoids

51
Q

def: 8-30 amino acids in length, containing proline and positively charged amino acids (arginine and lysine)

A

NLS (nuclear localization signal)

52
Q

def: ligands that mediate the opening of Na+ channels

A

neurotransmitters

MBB 231 (19 decks)

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