Basic Pathways Regenerative Biology & Medicine 568

Front 1

What are the 6 major signaling/receptor pathways in Embryonic development & AS cells

Back 1

1. Notch Pathway
2. Canonical Wnt Pathway
3. hedgehog Pathway
4. RTK pathway
5. TGF-beta pathway
6. JAK-STAT pathway

Front 2

Notch basics

Back 2

tells stem cells to remain stem cells

Juxtacrine signaling

Notch is a monomeric transmembrane receptor

Front 3

Notch ligands

Back 3

1. Delta
2. Jagged
3. Serrate

Front 4

Notch Intracellular Domain (NICD) interacts with __

Back 4

RBP-Jkappa (DNA binding protein)

histone acetyltransferases (HAT)
1. p300
2. PCAF

Front 5

Numb

Back 5

intracellular membrane- associated protein
inhibits Notch ICD separation

Numb causes daughter to differentiate

Front 6

how is Numb regulated

Back 6

in self renewing daughter cell numb is regulated at the transcriptional level by RNA binding protein
- Humans: NRP-1
- Drosophila: Musashi-1

Front 7

Notch Pathway walk through when Musashi is present

Back 7

ligand binds Notch receptor --> Presenelin cleaves ICD

Musashi binds Numb mRNA stopping translation

NICD -> nucleus interacting w/RBP-Jkappa, p300, & PCAF

--> transcribes proteins that repress genes for cell differentiation

Front 8

Canonical Wnt basics

Back 8

paracrine signaling

Tcf 1-3 & Lef-1 transcritional repressors that maintain AS cells, but with Wnt signal they become transcriptional activators

Front 9

Canonical Wnt receptor

Back 9

Receptor: Frizzled (Fz)

Co-Receptor: LRP-5/6

Front 10

how is Wnt inhibited

Back 10

Competitive inhibition by Fz- like proteins

Dickopf-1 binds LRP-5/6

Front 11

Canonical Wnt Pathway without Wnt

Back 11

Beta-Catenin binds to GSK-3 which is complexed with APC & axin

Beta Catenin is broken down by the proteasome APC

Front 12

LRP5/6

Back 12

Co-Receptor
binds Wnt

Front 13

Wnt

Back 13

binds Fz receptor & LRP5/6 co-receptor
--> activates PAR-1

Front 14

PAR-1

Back 14

Activated when Wnt binds Fz & LRP5/6

P-lates Disheveled

Front 15

Disheveled

Back 15

activated after P-lated by PAR-1

--> Inhibits GSK-3

Front 16

Canonical Wnt pathway: walkthrough w/out Wnt

Back 16

Beta-Catenin binds GSK-3 & is degraded by the the proteasome complex consisting of GSK-3, axin, & APC

Lef-1 & Tcf1-3 inhibit transcription of genes that activate Stem Cells

Front 17

Canonical Wnt pathway: walkthrough w/Wnt

Back 17

1. Wnt binds Fz & LRP5/6
2. --> PAR-1 to P-late Disheveled
3. Disheveled inhibits GSK-3
4. Beta-Catenin complexes w/ transcription factors Lef-1 & Tcf1-3
--> initiates transcription of genes that activates SC -> asymmetrically divide

Front 18

what are the hedgehog family of sinaling molecules?

*from book

Back 18

Sonic hedgehog (Shh)

Indian hedgehog (Ihh)

Desert hedgehog (Dsh)

Front 19

Hedgehog Pathway receptor?

Back 19

Patched

Front 20

what does Patched do?

Back 20

Hedgehog receptor

w/out Shh: bound to & inhibits Smoothened (Smo)

Shh-Patched --> activates Smo

Front 21

Smoothened (Smo)

Back 21

Hedgehog pathway

Shh-Patched cause P-lation --> activates Smo
-->inhibits proteins that cleave C-Term of Gli 2 & 3

Front 22

w/out Shh what are the TF in play? How are they modified? What do they do?

Vertebrates

Back 22

Gli 2 & Gli3

removal of their C-Term domain

represses transcription

Front 23

w/out Shh what are the TF in play? How are they modified? What do they do?

Drosophila
*from book

Back 23

Cubitus interruptis (Ci)

C-Term domain clipped

represses transcription

Front 24

w/Shh what are the TF in play? How are they modified? What do they do?

Vertebrates

Back 24

Gli1 & Gli2

Lance: check to see if any modification occurs

activates transcription

Front 25

w/Shh what are the TF in play? How are they modified? What do they do?

Drosophila

Back 25

Cubitus interruptis (Ci)

entire Ci is released from microtubule

activates transcription

Front 26

walk through hedgehog pathway w/out Shh

Vertebrates

Back 26

Patched inhibits Smo

Gli2/3 repress transcription by removal of their C-Term domains

Front 27

walk through hedgehog pathway w/Shh

Vertebrates

Back 27

1. Shh-Patched --> activates Smo
2. Smo is P-lated
3. Gli1/2 activate transcription

Front 28

What is special/different about Shh pathway?

Back 28

Shh signal inhibits action of receptor

Front 29

Short version of RTK pathway

Back 29

1. growth factor (EGF) binds RTK --> receptor dimerizes
2. activates ras
3. ras activates MAPKK Kinase -->->
4. MAPK activates transcription factors for growth & Differentiation

Front 30

what are the ligands in the JAK-STAT pathway?

Back 30

growth factors & cytokines

Front 31

what happens to receptor after ligand binds in JAK-STAT pathway?

Back 31

dimerization of receptor

JAK P-lates receptor Tyrosines--> activating Tyrosine Kinase

Front 32

walkthrough JAK-STAT pathway

Back 32

1. ligand binds receptor causing dimerization
2. JAK P-lates receptors' Tyrosines --> activating receptors Tyr Kinase
3. STAT docks on JAK
4. receptor P-lates STAT
5. STATs can form homo/heter dimer TF & initate Transcription of proliferation & differentation genes

Front 33

TGF-β pathway ligands

Back 33

TGF-β, Activin, & Nodal subfamily

BMP, GDF, & MIS subfamily

Front 34

TGF-β pathway receptor

Back 34

transmembrane protein Type I: 7

transmembrane protein Type II: 5

ligand binding causes heterodimer I:II & II P-lates I activating it's kinase domain

Front 35

Smad classes

Back 35

Receptor: 1-3, 5, 8

Co-Smad: 4 (only found in nucleus)

Inhibitory: 6, 7

Front 36

TGF-β pathway: TGF-β/Activin/Nodal ligand binding causes?

Back 36

cause 3 Type I to P-late (activate kinase)
--> P-late Smads 2/3 --> nucleus & complex w/Smad 4

Front 37

TGF-β pathway:BMP, GDF, & MIS ligand binding causes?

Back 37

causes 4 Type I to P-late (activate Kinase)
--> P-late Smads 1/5/8 --> nucleus
--> complex w/Smad 4
--> activate & INHIBIT transcription of genes

Front 38

These epithelial structures undergo maintenance & injury-induced regeneration through activation of resident ASCs

Back 38

Epidermis
Hair
cornea