01-27: Signaling Pathways Flashcards

1
Q

What are the 4 signaling factor families?

A
  • transforming growth factor b
  • fibroblast growth factor
  • hedgehog
  • Wnt
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2
Q

What are included in the transforming growth factor b family?

A
  • TGF-b1&raquo_space; TGF-b5
  • Activin
  • Inhibin
  • Mullerian inhibiting substance
  • Decapentaplegic
  • Vg1
  • BMP-1&raquo_space; BMP-15
  • Nodal
  • Glial cell line-derived neurotrophic factor
  • Lefty
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3
Q

What is TGF-b synthesized as?

A

a pair of inactive 390 amino acid precursors with a large proregion and a bioactive region

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4
Q

What is the large proregion of the TGF-b enzymatically cleaved from?

A

the bioactive region

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5
Q

How many proregion and bioactive regions are secreted from TGF-b?

A

2 proregions

2 bioactive regions

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6
Q

Which regions of TGF-b form a dimer?

A

the 2 bioactive regions

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7
Q

When is the TGF-b activated?

A

when proregions are separated from the bioactive dimer

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8
Q

What is the function of the bioactive dimer of TGF-b?

A

acts as a signaling molecule

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9
Q

What are the modes of action of bone morphogenic proteins (TGF-b family)?

A
  • Inhibit other processes in the embryo
  • Act by being inhibited by another molecule (in development of CNS)
  • Bind to bioactive dimers and prevent them from binding to receptors

**Inhibit the inhibitors&raquo_space; activates whatever the bone morphogenic proteins were inhibiting

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10
Q

What are 3 ways the fibroblast growth factor family regulate?

A
  • Modification of interaction with heparan proteoglycans in the receptor complex
  • Regulation at membrane of responding cell via actions of transmembrane proteins
  • Regulation by various molecules that complex with various parts of the signal transduction machinery
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11
Q

What does the Hedgehog family relate to?

A

the segment polarity molecule in Drosophila

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12
Q

What 3 factors does the Hedgehog family include?

A
  • Desert
  • Indian
  • Sonic hedgehog
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13
Q

What does the Wnt family relate to?

A

the segment polarity gene in Drosophila

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14
Q

What does the Wnt family often interact with?

A

components of extracellular matrix

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15
Q

What does the cytoplasmic domain of the receptors for fibroblast growth factors possess?

A

tyrosine kinase activity

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16
Q

What does the cytoplasmic domain of the receptors for TGF-b possess?

A

serine/threonine kinase activity

17
Q

What are 6 signaling pathways?

A
  • Delta-Notch pathway
  • Receptor tyrosine kinase pathway
  • Hedgehog pathway
  • Wnt signaling pathway
  • MicroRNA pathway
  • Retinol pathway
18
Q

What are the 2 components of the Delta-Notch pathway?

A
  • On dominant cell = Delta (signal molecule)

- On neighboring cell = Notch receptor

19
Q

What are the steps of the Delta-Notch pathway?

A

1- proteolytic cleavage of Notch intracellular domain

2- Notch intracellular domain complexes with Deltex

3- Complex enters nucleus (translocation)

4- Complex binds to Suppressor of Hairless

5- Notch-Deltex-Suppressor of Hairless complex binds to Enhancer of Split

6- Inhibitory signal represses gene expression

20
Q

What is lateral inhibition?

A

a type of signaling between a dominant cell and a neighboring cell

neighboring cells will become something different than their environment

21
Q

What is a dominant cell?

A

a cell in a population that begins to differentiate along a particular path

22
Q

What uses the receptor tyrosine kinase pathway?

A

fibroblast growth factor signaling molecules

23
Q

What are the steps of the Receptor Tyrosine Kinase pathway used by Fibroblast growth factor signaling molecules?

A
  • FGF binds to receptor tyrosine kinase
  • G protein = activated
  • Activation of RAS, RAF, MAP kinase, ERK
  • ERK translocated to nucleus
  • Various transcription factors = activated
24
Q

What are the steps of the Receptor Tyrosine Kinase pathway used by TGF-b?

A
  • TGF-b binds to serine/threonine kinase receptor type II
  • Receptor type II dimerizes with Receptor type I
  • Activation and dimerization of R-Smad, Co-Smad
  • Smad dimer translocates to the nucleus
  • Binds to co-factors
  • Co-factors bind to DNA regulatory factors
25
Q

What are the steps of the Hedgehog pathway?

A
  • Shh protein = complexed with cholesterol after being translated in sending cell
  • Dispersed translocates Shh-cholesterol to cell surface
  • Shh-cholesterol inhibits the inhibitory actions of Patched on Smoothened on the target cell (turns on Smoothened)
  • Uninhibited Smoothened signals complex on microtubules to release the transcription factor Gli
  • Gli translocates to the nucleus
  • Gli influences gene expression
26
Q

What are bound to an intracellular destruction complex within the target cell when there is no Wnt?

A

b-catenins

27
Q

What are the steps of the Wnt signaling pathway?

A
  • Wnt molecule binds to Frizzled on taget cell
  • Frizzled interacts with intracellular Disheveled
  • Disheveled prevents degradation of the b-catenins by the destruction complex (b-catenins now free)
  • b-catenins translocated to nucleus
  • b-catenins activate transcription factors
28
Q

What are MiRNAs?

A

small non-coding RNAs that influence gene expression

29
Q

What are the 2 major groups of MiRNAs?

A
  • Piwi-interacting RNAs (piRNAs)

- Endogenous small interfering RNAs (endo-siRNAs)

30
Q

When do piRNAs act?

A

during gametogenesis

31
Q

When are endo-siRNAs expressed?

A

in somatic tissues throughout development

32
Q

What are the steps of the microRNA pathway?

A
  • Double helical miRNA precursor molecule cleaved by Dicer
  • miRNA now active
  • Complexed with AGO protein
  • Complex approaches target mRNA
  • Cleaves target mRNA molecule
  • mRNA molecule now inactive
33
Q

What are the steps of the Retinol pathway?

A
  • Retinol (vitamin A) signal molecule binds to extracellular retinol-binding protein (RBP)
  • Retinol RBP complex binds to membrane RBP
  • Retinol released into cytoplasm
  • Cytoplasmic retinol binds to CRBP1
  • Enzymatic formations
  • Retinoic acid bound to CRABP1 and translocated into nucleus
  • Retinoic acid binds to dimer RXR-RAR
  • RXR-RAR binds to RARE
  • RARE activates transcription