Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

BMS 242 - Principles of Developmental Biology > Cell-cell interactions: TGFbeta and FGF signalling > Flashcards

Cell-cell interactions: TGFbeta and FGF signalling Flashcards

You may prefer our related Brainscape-certified flashcards:
AP® Biology flashcards Biology 101 flashcards
1
Q

What are the 3 common features in signal transduction pathways?

A

1) Reception
2) Transduction
3) Response

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What happens in the reception stage of a transduction pathway?

A

Ligand binds to a cell surface receptor and activates it

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What can a ligand be?

A

Extracellular or membrane bound

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What happens in the transduction stage of a transduction pathway?

A

Signal is relayed from the membrane to the nucleus

Via a cascade of secondary messengers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What happens in the response stage of a transduction pathway?

A

Transcription factor is activated:

  • Translocates into the nucleus
  • Induces transcription of specific target genes (to activate or repress genes)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What 3 families of molecules fall into the ‘TGF beta superfamily’?

A

1) BMP-like family
2) GDNF family
3) TGF-beta-like family

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are the members of the BMP-like family of TGF beta molecules?

What are they involved in?

A
  • BMP
  • GDF

Involved in development

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the members of the TGF-beta-like family of TGF beta molecules?

What are they involved in?

A
  • TGF-beta
  • Nodal
  • Activin
  • Veg1

Important role in cancer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What do the members of the TGF beta superfamily share?

What is the exception?

A

The same mechanism of signal transduction

With the exception of the SMAD proteins that are used - different receptors, different SMAD proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Describe the signalling transduction cascade of TGF beta

A

1) Ligand encounters receptor - first binds to type II receptor

2) Causes the receptor to undergo oligomerisation
- Bings in type I receptor
- Forms dimer with type II receptor

3) Dimer results in the activation of the type II receptor
4) Phosphorylation of type I receptor - triggers overall activation of the receptor
5) Specific SMAD proteins recruited and phosphorylated by the activated receptor
6) SMADs are further activated by SMAD 4 - resulting in an active complex that acts as a transcription factor
7) TF translocates into the nucleus - activating transcription

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What activity does the type II receptor have?

What does this promote?

A

Kinase activity

Promotes the phosphorylation of the type I receptor, triggering the overall activation of the receptor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the type II receptor of TGF beta?

Type I receptor?

A

TGFBR2

TGFBR1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What results in activation of the type II receptor?

A

Oligomerisation of type I and type II receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the SMAD proteins that are recruited and phosphorylated by the receptor in the case of TGF-beta ligand?

A

SMAD 2

SMAD 3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the SMAD proteins that are recruited and phosphorylated by the receptor in the case of BMP or GDF ligand?

A

SMAD 1
SMAD 5
SMAD 8

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How is BMP signalling controlled?

A

Through INHIBITION:
- Regulated extracellularly by antagonists

  • Modulate the amount of interaction that BMP and their receptors have
  • Different cell fates are dependant on the amount of ANTAGONIST present
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are the antagonists that control BMP signalling?

A
  • Chordin
  • Noggin
  • Follistatin
  • Cerberus
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Why is BMP signalling tightly regulated?

How is this easily done?

A

Want SPECIFIC cells to respond to signal at a SPECIFIC time and a SPECIFIC place

Easily done by having the components of the signalling pathway present but controlling the activity of these proteins through EXTRACELLULAR INHIBITORS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

How many families of RTK are there?

What does each family have different?

A

20 families

Each have individual receptors and ligand partners

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are examples of RTKs?

A
  • Insulin receptor
  • NGF receptor
  • PDGF receptor
  • FGF receptor
  • EGP receptor
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

How do RTKs and their ligands interact?

A

Some ligands - specific to one receptor, or bind to many

Some receptors - specific to one ligand, or to many

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What are 4 common features of all RTKs?

A
  • Mostly monomers (except insulin receptor)
  • Extracellular domain varies greatly
  • Intracellular domain has kinase activity
  • Short, single transmembrane domain
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Even though the extracellular domains of RTKs vary greatly, what can be seen?

A

Recognisable features, like the presence of immunoglobulin domains

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

How can the kinase domain of an RTK be split?

A

Into 2 domains

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Describe canonical RTK activation

A
  • Ligand dimerises and facilitates dimerisation of receptor

- Once positioned correctly, the kinase domains of the receptors phosphorylate each other (cross-phosphoylation)

26
Q

How is the dimerisation of RTK receptors different to TGF-beta receptor?

A

RTK:
- Dimerisation happens simultaneously, through the binding of a ligand

TGF-beta:
- Ligand binds one receptor and recruits the other

27
Q

What 3 things does ‘cross phosphorylation’ of the RTKs cause?

A

1) Increases ACTIVITY of the kinase
2) STABILISES the receptor in an active state (ligand independant)
3) Allows the kinase to PHOSPHOYLATE other TYROSINES in the RECEPTOR - creating docking sites

28
Q

What are the docking sites on the intracellular portion of RTKs for?

A

Recruitment of secondary messengers

29
Q

How does the phosphorylated tyrosine receptor transduce the signal?

A
  • Phosphorylated tyrosine acts as a docking site for downstream proteins
30
Q

How do downstream proteins recognise the docking sites on RTKs?

A

Contain SH2:

  • Recognises the phoshotyrosine
  • Recognises glutamic acid - glutamic acid - isoleucine
31
Q

Name 3 proteins that bind to RTKs

A

1) PI 3-kinase
2) GTPase - activating protein (GAP)
3) PLC-gamma

32
Q

What pathway is PI 3-kinase involved in?

A

Inositol

33
Q

What pathway is GAP involved in?

A

RAS/MAP-kinase

34
Q

What pathway is PLC-gamma involved in?

A

Inositol

35
Q

When is ras active?

A

When it is bound to GTP

36
Q

What is ras inactive?

A

When it is bound to GDP

37
Q

What system is needed for ras activation and why?

A

A system to propagate the activation of ras in a more STABLE manner

As when GTP is bound by ras it is rapidly hydrolysed - not active for very long

38
Q

What is Raf?

What is it activated by?

A

Map- KKK

Activated by GTP ras

39
Q

What is Mek activated by?

A

Through phosphorylation by Map-KKK (Raf)

40
Q

What is MapK activated by?

A

Dual phosphoylation of SERINE and THREONINE (separated by one amino acids) by Map-KK (Mek)

41
Q

How many members of FGF ligands are there?

A

22 members

42
Q

What are FGFs important in?

A

Embryonic development

43
Q

What types of molecules are FGF ligands?

A
  • Small groups of endocrine, juxtacrine FGFs

- Very large group of paracrine FGFs

44
Q

Describe the expression of some FGFs?

A

Very DISCRETE

45
Q

When does FGF8 play an important role?

What does FGF8 play a role in?

A

During development

  • Patterning the midbrain-hindbrain boundary
  • Patterning somites
  • Patterning the developing limb bud
46
Q

Where is FGF8 present?

What does it do?

A
  • At the midbrain-hindbrain boundary
  • Strong expression in the developing limb bud field
  • Specific, segmented pattern of expression in the developing SOMITES
47
Q

What is the FGF receptor family characterised by?

A

3 repeat structures in the extracellular domain:

- D1, D2, D3

48
Q

What are the D1, D2 and D3 structures in the extracellular domain of FGF receptor superfamily?

A

Immunoglobulin like domains

49
Q

Where do ligands bind to in the FGF receptor?

A

D2 and D3 repeat

50
Q

What kind of receptor is an FGF receptor?

A

RTK

51
Q

How many transmembrane domains do FGF receptors have?

A

1

52
Q

How many FGF receptors trigger the effect of the 22 FGF ligands?

What does this mean?

A

4

One FGF receptor binds to MANY FGF ligands

53
Q

What dictates the specificity of the FGF signalling pathway?

A
  • FGF receptors must form complexes with HSPGs to be able to signal
  • HSPGs have specific structures
54
Q

What do HSPGs modify?

A

Extracellular cell-cell signalling

55
Q

What is the structure of HSPGs?

How does this confer specificity to FGF signalling?

A
  • Protein core
  • Large sugar chains of heparin attached to the protein core
  • Each sugar chain can be modified by sulphation
  • Results in a ‘code’ that creates binding sites for specific proteins (eg. FGF2)

SO, have distinct protein core, distinct sugars attached and distinct sulphation modifications

56
Q

How can the different protein cores of HSPG be arranged?

A

3 different types:

  • Transmembrane
  • Tethered
  • Secreted
57
Q

How do the FGF family of receptors transduce the signals?

A

Through distinct secondary messengers

58
Q

What does the downstream effect of the FGF receptor depend upon?

A

Different depending on the secondary signals that are activated

Same ligand/receptor set can trigger COMPLETELY different responses, depending on the secondary messengers activated

59
Q

What does the Map kinase pathway lead to?

How is this different to other secondary messengers?

A

Cell proliferation

Other secondary messengers lead to cell survival or cell motility

60
Q

What are mutations in the extracellular domain of the FGF receptors result in?

A

Human disease

61
Q

What does a mutation in FGFR3 result in?

A

Achondroplasia - congenital birth defect

62
Q

Why do we need to have an understanding of receptors/ligand functioning and signalling?

A

Can better understand what does wrong when have mutations effecting particular receptors

BMS 242 - Principles of Developmental Biology (16 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions