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

L10 - TGF-B and FGF Signalling Flashcards

(63 cards)

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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
When is Ras ON/OFF
ON with GTP bound | OFF with GDP bound
26
What switches Ras ON
GEF
27
What switches Ras OFF
GAP
28
Activated Ras is stable?
No is very unstable
29
MAP-KKK MAP KK MAP K Are all also known as
Raf Mek Erk
30
Describe what happens when Ras is activated
Activation of MAP KKK MAP KKK phosphoryated MAP KK MAP KK phosphorylates MAP K MAP K phosphorylates target proteins or transcription factors
31
What are the two terminal effects of activation of the Ras pathway
Changes in protein function | Changes in gene expression
32
What is unusual RE MAP K
Activation by dual phosphorylation of a serine and a threonine separated by a single amino acid
33
FGF family contains how many members
22
34
How many broad groups of FGF ligands - name them
3 Endo, intra and paracrine
35
Describe expression of FGF8 in developement
Mid-brain hind-brain boundary Developing limb bud field Segmented expression in the somites
36
How many receptors for all of the FGFs
4
37
Alternative splicing of FGF R creates how many isoforms
48
38
What domains do FGF receptors contain
Immunoglobin like domains
39
What domains do ligands bind to
D2 and D3
40
Acid box has a role in
Negative regulation
41
What do FGFs have to first bind to inordere to be able to activate the receptor
HSPGS
42
HSPGS are
Heparan sulphate proteoglycans
43
What parts of HSPGs do FGFs bind to
Gkycosaminoglycans
44
Three types of protein core in HSPGs
Trnasmmebrane Tethered Secreted
45
What are the ways in which HSPGs can be modified
Sulphation
46
What is the charge on HSPGs
Polyanionic - net negative charge
47
What is the main effect of FGF signalling via the RAS GTPase pathway
Cell proliferation
48
What is the main effect of FGF signalling via the Pi3 kinase
Cell survival
49
What is the main effect of FGF signalling via the PL-gamma
Cell motility
50
Mutations in FGFR1 can cause what diseases
Pfeiffer sydrome
51
Mutations in FGFR2 cause diseases such as
Pfeiffer synd Apert synd Crouzon synd Jackson-weiss syndrome
52
Mutations in FGFR3 causes what diseases
Thanatophoric dysplasia | ACHONDROPLASIA
53
Three main classed of TGF-B
BMP GDNF TGF-B
54
Examlpes of members of BMP family
BMPs GDFs AMH
55
Examples of GDNF members
GDNF. artemin, neuturin, persephin
56
Examples of TgfB
Activin Nodal Veg1
57
Describe TGF-B signalling
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
The EC domain of TGF-B R is modulated by many what Give examples
ANTAGONISTS Noggin, chordin and follistatin
59
What SMAD is common for all
SMAD 4
60
What SMAD for TGF-B
2 5
61
What SMAD for BMP and GDF
1 5 8
62
Control of BMP signaling operated through
Inhibition by many antagonists Cereberus Follistatin Chordin Noggin
63
What does SMAD 6/7 do
Inhibits the phosphorylation of SMAD 1 5 8

BMS242 Developmental Biology (17 decks)

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