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Embryology Test 1 KLS > Lecture 8: Signaling Pathways > Flashcards

Lecture 8: Signaling Pathways Flashcards

1
Q

Signaling Factor Families

A
  • Transforming Growth Factor-β Family
  • Fibroblast Growth Factor Family
  • Hedgehog Family
  • Wnt Family
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2
Q

Transforming growth Factor-beta Family:

A

TGF- β1 … TGF- β5

Activin

Inhibin

Mullerian inhibiting substance

Decapentaplegic

Vg1

BMP-1…BMP-15

Nodal

Glial cell line-derived neurotrophic factor

Lefty

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3
Q

TGF-Beta 1

A

Disulfide-linked dimer

Synthesized as a pair of inactive 390 amino acid precursors:

  • Consists of a large proregion and a bioactive region
  • The large proregion is enzymatically cleaved from the bioactive region.
  • Two bioactive regions and two proregions are secreted.
  • Two bioactive regions form a dimer
  • The proregions complex with the bioactive dimer and maintain it in a latent form.
  • Activation occurs when the proregions are separated from the bioactive dimer.
  • Bioactive dimer functions as a signaling molecule.
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4
Q

Bone morphogenetic proteins:

A

• Encompasses 15members

• Modes of action:

  • Often inhibit other processes in the embryo
  • Often act by being inhibited by other molecules (i.e., in the development of the CNS)
  • Bind to bioactive dimers and prevent them from binding to receptors

*• Refer to Table 4.2 for molecules that are antagonistic to BMPs *

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5
Q

Fibroblast Growth Factor Family

A

22 members

Means of regulation:

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 transductoy machinery.

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6
Q

Hedgehog Family:

A
  • Related to the segment polarity molecule in Drosophila
  • Includes: Desert, Indian and Sonic Hedgehog
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7
Q

Wnt Family:

A
  • 18 members
  • Related to segment polarity gene in Drosophila
  • Often interacts with components of extracellular matrix
  • Plays different roles in various vertebrate classes
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8
Q

Receptor Molecules

A

Intracellular Receptors, Cell Surface Receptors

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9
Q

Cell Surface Receptors:

A

Receptors wtih intrinsic protein kinase activity:

Includes receptors for fibroblast growth factors

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10
Q

Receptor Molecules:

A

Intracellular receptors
Cell surface Receptors:

  • Includes receptors for fibroblast growth factors
    • Cytoplasmic domain possesses_ tyrosine kinase activity_
  • ​Includes receptors for TGF-Beta Factors:

​Cytoplasmic domain possesses serine/threonine kinase activity

  • ​Receptors that utilize a second messenger system: cAMP, cGMP, Gprotiens
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11
Q

List 6 Examples of Signaling Pathways:

A
  1. Delta-Notch
  2. Receptor Tyrosine Kinase Pathway
  3. Hedgehog Pathway
  4. Wnt signaling
  5. MicroRNA pathway
  6. Retinol Pathway
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12
Q

Delta-Notch Pathway:

A
  • Delta (signal molecule) on dominant cell
  • Notch receptor on a neighboring cell
  • Proteolytic cleavage of Notch inracellular domain
  • Notch intracellular domain comples with Deltex
  • Complex enters nucleus
  • Complex binds to Suppressor of hairless
  • Notch-Deltex-Suppressor of hairless complex binds to Enhancer of split
  • Resultant inhibitory signal represses gene expression

SEE 4-14

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13
Q

Lateral Inhibition:

A

Type of signaling between a dominant cell and neighboring cell

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14
Q

Dominant cell refers to:

A

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

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15
Q

Dominant cell expresses:

A

Delta signaling molecules on its cell membrane. Delta then binds to Notch receptors on neighboring cells and, via the Delta-Notch pathway, represses genes in the neighboring cells.

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16
Q

The Receptor Tyrosine Kinase Pathway is utilized by:

A

fibroblast growth facor signaling

17
Q

Pathway components and actions of the Receptor Tyrosine Kinase Pathway:

A

FGF binds to receptor tyrosine kinase

G protein is activated which leads to:

  • ​Activation of pathways components: RAS, RAF, MAP kinase, and ERK

ERK translocates to nucleus and activates various transcription factors.

18
Q

Receptor Tyrosine Kinase Pathway

Utilized by Transforming:

A

growth factor-beta signaling molecules.

19
Q

Pathway components and actions (Transforming Growth factor beta)

A

Pathwaycomponentsandactions:

• TgF-βbindstoserine/threoninekinasereceptortypeII.

  • ReceptortypeIIdimerizeswithreceptortypeI.
  • Activationofpathwayscomponents:R-SmadandCo-Smadwhich

dimerize

• Smaddimertranslocatestonucleusandbindstoco- factors which can then bind to DNA regulatory factors.

20
Q

Pathway components and actions of the Hedgehog Pathway:

A
  • Sonic hedgehog protein is complexed with cholesterol shortly after being translated in sending cell.
  • Shh-cholesterol is translocated to cell surface via the action of Dispersed (product of dispersed gene).
  • Shh-cholesterol inhibits the inhibitory actions of Patchedon Smoothened on the target cell.
  • Uninhibited Smoothened signals the release of transcription Gli from a complex on microtubules.
  • Gli translocates to the nucleus and influences gene expression.
21
Q

Wnt Signaling Pathway:

in the absense of WNT, what are bound to an intracellular destruction complex within the target cell?

A

Beta-catenins

22
Q

Wnt Signaling Pathway components and actions:

A

Wnt molecule (ligand) binds to Frizzled on target cell

Frizzled interacts with intracellular Disheveled.

Disheveled prevents the degredation of the beta-catenins by the destruction complex.

Beta-catenins translocate to the nucleus and activates transcription factors.

23
Q

Small RNAs(MiRNAs) are:

A

small noncoding RNAs that influence gene expression

24
Q

Two major groups of MiRNAs:

A

Piwi-interacting RNAs (piRNAs):
Act during gametogenesis (esp. spermatogenesis)

Endogenous small interfering RNAs (end-si-RNAs): Expressed in somatic tissues throughout development

25
Q

Roles of Dicer and Argonaute (AGO) protein in MicroRNA Pathway

A

The double helical precursor molecule, often containing a hairpin loop, is cleaved by Dicer, reculting in a small miRNA molecule, which is then complexed with an Argonaute (AGO) protein. THis complex approaches the target mRNA and through its intrinsic RNase activity. It cleaves the target mRNA molecule, thereby inactivating it.

26
Q

Retinol Pathway components and actions:

A

• Retinol(vitaminA)asasignalmoleculebindstoan extracellular retinol-binding protein (RBP).

Theretinol-RBPcomplexbindstoamembraneRBP.

Retinolisreleasedintothecytoplasmandbindstoa

CRBP 1.

  • After a series of enzymatic transformations,retinoic acidis bound to CRABP 1 and translocated into the nucleus.
  • Retinoic acid binds to the dimer RXR-RAR which binds to RARE which activates transcription.
27
Q
A

Embryology Test 1 KLS (8 decks)

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