Lecture A3 Flashcards
To properly establish cell fate and diversity, cells need to do what?
properly communicate
Cell diversity in the human body is driven by two events: ______
cell intrinsic & cell extrinsic events
The most common extrinsic event that drives cell diversity is _______
cell-cell signalling
Types of extracellular signals
1) Constitutive signals
2) Mitogens
3) Differentiation signals
4) Apoptotic signals
Constitutive signals do what?
maintains the cell
Mitogens do what?
tell cells to divide
Differentiation signals do what?
tell cell to differentiate
Apoptotic signals do what?
tell cells to die
Types of cell-cell communication
1) Autocrine
2) Paracrine
3) Juxtracrine
4) Endocrine
Autocrine signaling (def.)
cell secrete signaling molecules that act on the cell that secretes
Paracrine signaling (def.)
secretion of signaling molecules into extracellular where it acts on the surrounding cells; not contact dependent
Juxtacrine signaling (def.)
signaling molecules enter surrounding cells through gap junctions/ membrane nanotubes without secretion into ECM; contact-dependent
Endocrine signaling (def.)
signaling molecules are secreted into blood plasma/ECM to act on cells far from the cell that secreted it
Endocrine signaling is only for animals that _____
have a vasculature
_____ signaling encourages cells to respond coordinately
Autocrine/Paracrine
Most common example of endocrine signaling: ____
hormones
Most signaling molecules are _____ and cannot _____ so they ______
-hydrophilic
-cross the PM
-interact with cell surface receptors
Signaling molecules that are hydrophobic can ______ and do what? by?
-cross the membrane
-cause changes in TF activity
-pairing with intracellular receptor
example of hydrophobic signalling molecule receptor
steroid hormone nuclear receptor
Relay proteins do what?
pass the message to the next component (protein)
Messenger proteins do what?
pass the message to a another part of the cell (ex. cytosol to nucleus)
Adaptor proteins do what?
connect one signaling protein to another without a signal
Scaffold proteins are ____
a type of adaptor protein that attaches multiple proteins together
Amplifier proteins do what?
increase the signal that they receive by producing a lot of intracellular mediators or activating a lot of downstream signaling proteins
Transducer proteins do what?
convert the signal into a different form (ex. Phosphorylation signal is used to create cAMP that activates downstream)
Signaling cascade is _____
multiple amplification steps
Bifurcation proteins do what?
spread the signaling from one pathway to another
Integrator proteins do what?
receive signals from two or more signaling pathways and integrate` them
Latent gene regulatory proteins do what?
activated at cell surface by activated receptors then move into the nucleus to stimulate transcription
Latent gene regulatory proteins are ____
TF that are part of the receptors
Two receptor signals can be integrated if _____
-both are needed to activate the same protein
-they activate proteins that interact to propagate downstream signals
general pathway steps
1) ligand
2) receptor
3) effector
4) target
NOTCH pathway ligand
DELTA
NOTCH pathway receptor
NOTCH
NOTCH pathway effector
NICD
NOTCH pathway is a ______ signaling pathway
paracrine
NOTCH pathway steps
1) Delta (attached to adjacent cell) interacts with NOTCH receptor on it EGF-like domains
2) NOTCH receptor (already cleaved at site 1 in the golgi) is cleaved at site 2 and 3 to release NICD tail
3) NICD tail acts as a messenger that goes to nucleus as TF
NICD is a part of ______
NOTCH receptor that is cleaved when activated by DELTA
TGF-B pathway ligand
TGF-B
TGF-B pathway receptor
TGFBR
TGF-B pathway effector
SMAD
TGF-B pathway feedback mechanism
target inhibits TGF-B (ligand) & SMAD (effector)(suppress autocrine signaling)
TGF-B pathway steps
1) TGF-B binds to type II receptor which recruits and phosphorylates type I receptor
2) type I receptor phosphorylate to open smad 2/3 protein
3) smad 2/3 oligomerizes with smad 4
4) smad 2/3 - smad 4 complex migrates to nucleus and activates transcription of target genes
WNT pathway ligand
WNT
WNT pathway receptor
Frizzled & LRP (co-receptor)
WNT pathway effector
B-Catenin
WNT pathway transducer
GSK3B/Dishevelled
WNT pathway scaffold
axin
WNT pathway (without Wnt signal) steps
1) LRP & Frizzled receptor don’t dimerize
2) inactive dishevelled protein
3) active GSK-3B & unstable B- catenin (phosphorylated) held in complex by axin scaffold protein
3) phosphorylated B-catenin is ubiquitylated and degraded by proteasome
4)Wnt responsive genes are off
WNT pathway (with Wnt signal) steps
1) LRP & Frizzled receptor dimerize
2) activates dishevelled protein
3) active dishevelled protein inactivates GSK-3B & stable B- catenin is unphosphorylated and removed from complex with axin scaffold protein
3) unphosphorylated B-catenin enters nucleus
4)Wnt responsive genes are on
Hedgehog pathway ligand
hedgehog protein
Hedgehog pathway receptor
patched
Hedgehog pathway transducer
smoothened
Hedgehog pathway effector
GLIA/GLIR (Ci)
Hedgehog pathway steps (without HH signal)
1) Patched receptor represses smoothened
2) Costal adaptor protein holds Ci/GLI protein + suppressor of Fused + fused protein together
3)Ci protein is ubiquitylated and cleaved by proteasome to form GLIR (repressor)
4)Cleaved Ci + corepressor move to nucleus and repress target genes
Hedgehog pathway steps (with HH signal)
1) Patched receptor stops repressing smoothened
2) smoothened inhibits proteolysis of GLI and releases Costal adaptor protein + Ci/GLI protein + suppressor of Fused + fused protein complex from microtubule
3)Intact Ci protein (GLIA -activator) + co activator moves into nucleus and activates transcription of target genes
Fused and suppressor of fused do what?
modify GLI/Ci and lead to proteolytic cleavage
GLIA is _____
the activator form of GLI/Ci
GLIR is ______
the repressor form of GLI/Ci
_______ (FGF) and ________ (EGF) are part of a protein family of ______
-fibroblast growth factor
-epidermal growth factor
-growth factors
Growth factor receptors have these extracellular domains which help them to do what?
- cysteine-rich domain and immunoglobulin like domain
-allows them to bind to growth factors
Growth factor receptors have these intracellular domains which help them to do what?
-tyrosine kinase domain
-transduce signals into the cell
Growth factor (GF) signaling pathway ligand
FGF/EGF etc.
GF signaling pathway receptor
receptor tyrosine kinase (RTK)
GF signaling pathway: RTK signals ______
AKT & MAPK which signals other TFs
GF-RTK signalling pathway steps (MAPK)
1) ligand bind leads to clustering of receptors and autophosphorylation of receptor tyrosine kinase domain
2) Grb-2 adaptor protein binds to phos. domain which then binds to Ras-GEF
3) Ras-GEF turns Ras-GDP to Ras-GTP
4) Ras-GTP activates MAP KKK that activates MAP KK –> MAP K with ATP
5) MAP K activates other proteins
In GF pathway, RAS proteins acts as ______ to multiple signaling pathways
relays and transducers (GTP to phosphorylation)
nuclear hormone (steroid hormone) receptor signaling TF is _____
the steroid hormone + steroid hormone receptor
nuclear hormone receptor signaling: hormone-receptor complex does what in its early primary response?
-activates primary response genes in the nucleus
nuclear hormone receptor signaling: hormone-receptor complex does what in its delayed secondary response?
-primary response protein shuts off primary response genes and turn on secondary response genes to make secondary-response proteins
steroid hormones can ______ without ______
-cross the PM
-extracellular receptor
nuclear receptor superfamily have these domains: _____
-transcription-activating domain
-DNA-binding domain
-ligand-binding domain
DNA that binds nuclear receptor superfamily has this domain: _____
receptor-binding element near the target genes
6 types of nuclear receptor superfamily
1) cortisol receptor
2) estrogen receptor
3) progesterone receptor
4) vitamin D receptor
5) thyroid hormone receptor
5) retinoic acid receptor
Cell diversity in human body needs the production of diverse set of cells when?
-during early development and also during adult form for wound healing, hematopoiesis
hematopoiesis (def.)
blood cell production (all types of blood cell)
Neurogenesis (def.)
the process by which new neurons are formed in the brain
Neurogenesis involves _____ (general)
the inactivation of proliferative genes and activation of neurogenic genes
proliferative genes do what?
encourage the making of more precursor cells
TFs involved in neurogenesis
-Neurogenin 2
-Bcl6
-Sirt1
Neurogenin 2 is what?
An activating HLH (helix loop helix) transcription factor that promotes neurogenesis
Bcl6 is what?
A Zinc-finger transcriptional repressor
Sirt1is what?
A protein involved in epigenetic repression of
‘active’ chromatin
Actions of TFs in Neurogenesis
-Sirt1and Bcl6 turn off proliferative genes
-Neurogenin 2 turn on neurogenic genes
adipokines (def.)
signalling molecules secreted by adipocytes
preadipocytes are made from ______
mesenchymal stem cells and the absence of Wnt signals
adipogenic stimuli does what to preadipocytes?
-inhibit pre-adipocyte genes
-inhibit Wnt & B-catenin which normally inhibit further adipocyte differentiation
-activates adipocyte genes
how adipocyte genes are activated?
-adipogenic stimuli activates C/EBPδ/β which activates C/EBPδ/a & PPARγ which activate adipocyte genes
PPARγ is ______ with ______ as activating cofactor. It is highly expressed in _______.
-nuclear receptor
-fatty acids
-adipose tissues
“Master regulator” of adipogenesis
PPARγ
C/EBPδ/β is _______
-bZip protein
Function of C/EBP proteins
-integrate proliferation and differentiation genes
