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BMS242 Developmental Biology > L10 - TGF-B and FGF Signalling > Flashcards

L10 - TGF-B and FGF Signalling Flashcards

1
Q

Three common features of signalling pathways

A

Reception
Transduction
Response

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2
Q

How many families of RTKs

A

20

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3
Q

In the human genome how many RTKS identified

A

58

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4
Q

Ligands which are specific for one receptor are

A

High affinity

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5
Q

Ligands which are specific for many receptors are

A

Low affinity

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6
Q

All RTKS are ______mers except

A

Monomers

Except insulin receptor

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7
Q

What domains vary greatly RE RTKS

A

EC domains

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8
Q

What is the EC domain of an RTK responsible for

A

Ligand binding activity

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9
Q

How many TMDs does an RTK have

A

1

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10
Q

RTK ligands able to

A

Dimerise

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11
Q

Binding of ligand to RTK fascilitates

A

Receptor dimerisations

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12
Q

Once the receptor has dimerised and is positioned correctly describe what happens

A

Kinase domains phosphorylate each other

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13
Q

What is the effect of the kinase domains phosphorylating each other

A

Increases the activity of the receptor
Stabilises the receptor in the active state
Causes the kinase domains to phosphorylate other tyrosines in the receptor

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14
Q

What is the effect of other tyrosines in the receptor being phosphorylated

A

Creates binding sites for other proteins with an SH2 domain

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15
Q

Describe how a dominant negative receptor tyrosine kinase would be made

A

Created RTK mutated in the kinase doamin

Dimerise with wildtype receptors (with an active kinase domain - poisons the endogenous receptor

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16
Q

Describe how you would make a consitiutively active RTK

A

Make DNA for a normal receptor which lacks a ligand binding domain and instead has a homodimerisation domain
RTK dimers form in the absence of the ligand - LIGAND INDEPENDENT

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17
Q

What three types of signalling molecule bind to the phosphorylated receptor

A

PI3-kinase
GTPase activating protein
PLC-gamma

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18
Q

PI3 kinase and PLC-gamma are part of which pathway

A

Inositol lipid pathway

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19
Q

SH2 doamins in SRc recognise which short polypeptide

A

Phosphotyrosine, glutamic acid, glutamic acid, isoleucine

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20
Q

What two domains does GRB2 contain

A

SH2 and SH3

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21
Q

What is Sos

A

Guanine nucleotide exchange factor

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22
Q

What is the effect of binding of GRB2 and Sos

A

Couple the receptor to the inactive Ras

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23
Q

What does Sos promote

A

Dissociation of GDP from Ras

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24
Q

Once GDP dissociated from Ras what happens

A

GTP binds - dissociates from Sos

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25
Q

When is Ras ON/OFF

A

ON with GTP bound

OFF with GDP bound

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26
Q

What switches Ras ON

27
Q

What switches Ras OFF

28
Q

Activated Ras is stable?

A

No is very unstable

29
Q

MAP-KKK
MAP KK
MAP K

Are all also known as

A

Raf
Mek
Erk

30
Q

Describe what happens when Ras is activated

A

Activation of MAP KKK
MAP KKK phosphoryated MAP KK
MAP KK phosphorylates MAP K
MAP K phosphorylates target proteins or transcription factors

31
Q

What are the two terminal effects of activation of the Ras pathway

A

Changes in protein function

Changes in gene expression

32
Q

What is unusual RE MAP K

A

Activation by dual phosphorylation of a serine and a threonine separated by a single amino acid

33
Q

FGF family contains how many members

34
Q

How many broad groups of FGF ligands - name them

A

3

Endo, intra and paracrine

35
Q

Describe expression of FGF8 in developement

A

Mid-brain hind-brain boundary
Developing limb bud field
Segmented expression in the somites

36
Q

How many receptors for all of the FGFs

37
Q

Alternative splicing of FGF R creates how many isoforms

38
Q

What domains do FGF receptors contain

A

Immunoglobin like domains

39
Q

What domains do ligands bind to

40
Q

Acid box has a role in

A

Negative regulation

41
Q

What do FGFs have to first bind to inordere to be able to activate the receptor

42
Q

HSPGS are

A

Heparan sulphate proteoglycans

43
Q

What parts of HSPGs do FGFs bind to

A

Gkycosaminoglycans

44
Q

Three types of protein core in HSPGs

A

Trnasmmebrane
Tethered
Secreted

45
Q

What are the ways in which HSPGs can be modified

A

Sulphation

46
Q

What is the charge on HSPGs

A

Polyanionic - net negative charge

47
Q

What is the main effect of FGF signalling via the RAS GTPase pathway

A

Cell proliferation

48
Q

What is the main effect of FGF signalling via the Pi3 kinase

A

Cell survival

49
Q

What is the main effect of FGF signalling via the PL-gamma

A

Cell motility

50
Q

Mutations in FGFR1 can cause what diseases

A

Pfeiffer sydrome

51
Q

Mutations in FGFR2 cause diseases such as

A

Pfeiffer synd
Apert synd
Crouzon synd
Jackson-weiss syndrome

52
Q

Mutations in FGFR3 causes what diseases

A

Thanatophoric dysplasia

ACHONDROPLASIA

53
Q

Three main classed of TGF-B

A

BMP
GDNF
TGF-B

54
Q

Examlpes of members of BMP family

A

BMPs GDFs AMH

55
Q

Examples of GDNF members

A

GDNF. artemin, neuturin, persephin

56
Q

Examples of TgfB

A

Activin
Nodal
Veg1

57
Q

Describe TGF-B signalling

A

Ligand binds type II receptor
Causes oligomerisation with the type 1 receptor which is brought in
Dimer formation causes activation of the type 2 receptor which has kinase activity
Phosphorylation of type 1 receptor
Recruitment and phosphorylation of SMAD proteins forming a complex
Acts as a transcription factor

58
Q

The EC domain of TGF-B R is modulated by many what

Give examples

A

ANTAGONISTS

Noggin, chordin and follistatin

59
Q

What SMAD is common for all

60
Q

What SMAD for TGF-B

61
Q

What SMAD for BMP and GDF

62
Q

Control of BMP signaling operated through

A

Inhibition by many antagonists

Cereberus
Follistatin
Chordin
Noggin

63
Q

What does SMAD 6/7 do

A

Inhibits the phosphorylation of SMAD 1 5 8

BMS242 Developmental Biology (17 decks)

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