2.9: Signaling via Protein Modifications Flashcards
state and describe the two mechanisms of signaling via enzyme coupled receptors
- phosphorylation: signal perception triggers activation of receptor kinases or receptor associated kinases
- proteolysis: signal perception triggers protein cleavage or degradation
state the 3 examples of phosphorylation
- receptor tyrosine kinases
- tyrosine kinase associated receptors
- receptor serine/threonine kinases
describe the common structure of receptor protein kinases (RTKs) and their functions
- different ec domains bind different ligands
- has tm domain
- ic tyrosine kinase domain phosphorylate different targets at tyrosine residues
how are RTKs activated
- ligand binding (signal)
- transautophosphorylation
(trans = on diff RTK molecule, auto = RTKs can act as RTK)
state the structure of activated RTKs
dimers
t/f after signal proteins bind to RTKs, the transautophosphorylation must activate each others kinase domains are the same time
true
t/f the signal protein for RTKs don’t always have to be dimers
yes
RTK transautophosphorylation can recruit other signaling molecules, this means the acitvated RTK can act as what type of protein
scaffold protein
when rtks act as a scaffold, what do proteins bind to
phosphorylated tyrosine
which domains can signaling proteins bind to RTKs to
SH2 or PTB domains
explain how signaling proteins can bind to RTKs via SH2 or PTB domains
each SH2 domain has two binding sites for specificity: recognizes the phosphorylated tyrosine, recognizes nearby amino acids
these ensure that SH2 domains bind to specific phosphorylated proteins
t/f activated RTKs can recruit other signaling molecules and often activates Ras-GEFs
true
Ras family proteins are related to other monomeric ________
GTPases
Many RTKs signal to activate _____ monomeric GTPases
Ras
what are MAP kinase
mitogen activated protein kinase - signal that generates mitosis
do all MAP kinases activate mitosis
no
which cascade can activated ras activate
MAP kinase cascades
what can MAP kinases convert a short term RTK activation at the cell surface into
a stable/long term change in gene expression
which type of feedback do MAP kinases provide
negative feedback
How many of each of the following do humans have: MAPKKK (Raf), MAPKK (Mek), MAPK (Erk)
MAPKKK: ~7
MAPKK: 7
MAPK: 12
state what type of changes the effector proteins cause at the end of the MPA kinase cascade
- changes in protein activity (protein x, protein y)
- changes in gene expression (transcription reg prot A and B)
state what can provide specificity to MAP kinase cascades
scaffold proteins
drosophila sevenless signaling is an example of what
RTK signaling
Drosophila compound eyes are made of ___________
Each ommatidia has _ photoreceptor cells (R1-R_)
The R_ cells is required to detect UV light
ommatidia, 8, 7
which is the first cell to differentiate in the ommatidia (R what) and which is last
R8, R7
in sevenless signaling:
RTK = _________
Ligand = _________
Adaptor protein = _________
Ras-GEF = _________
RTK = Sevenless (Sev)
* Ligand = Bride of Sevenless (Boss)
* Adaptor protein = Grb2 (Drk)
* Ras-GEF = Son of Sevenless (Sos)
what is the end product of the sevenless signaling pathway
differentiation into R7
describe how RTKs can signal through phosphoinositides (PIPs)
- RTK activated
by a survival
factor - RTK activates
PI 3-kinase - PI 3-kinase converts PI(4,5)P2 to
PI(3,4,5)P3 - PDK1 & Akt bind PI(3,4,5)P3
- PDK & mTORC2 phosphorylate Akt
- Akt phosphorylates Bad to release
Bcl2 to inhibit apoptosis
(in order to survive = can’t die)
there can be cross talk between ?
RTK and GPCR signaling
what type of receptors have no kinase activity
cytokine receptors (no tyrosine kinase domain)
those receptors that have no kinase activity, they associate with what to be able to signal
cytoplasmic tyrosine kinase
which mechanisms remain similar between tyrosine kinase associated receptors and RTKs
transautophosphorylation and protein binding to the phosphorylated receptor
compare and contrast between receptor serine/threonine kinases and RTKs
Similar to RTKs:
* Extracellular ligand binding
domain
* Transmembrane domain
* Intracellular kinase domain
* Multiple receptors associate
in response to signals
But: kinase domains
phosphorylate serine and/or
threonine residues in targets
delta notch is an example of what type of signaling and notch signaling involves signaling via (2)
- contact dependent signaling
1. endocytosis
2. proteolysis
- where in the cell are notch proteins made and why
- where is notch cleaved into two pieces
- in the ER bc TM
- golgi
state the signifier of proper notch
the cleavage
do the cleaved pieces of notch stay together or go apart when they move to the plasma membrane
stay together
interaction with delta results in further/less notch proteolysis
further
the ______ part of notch directly interacts with delta on the surface of the other cell, delta notch is _______ into the delta expressing cell for proper gene expression and the remainder of notch is cleaved at ____ more sites
extracellular, endocytosed, two
after delta-notch is endocytosed into the delta expressing cell, the remainder of notch is cleaved at how many more sites
two
does the cytosolic head or tail of notch move to the nucleus and what does it promote
tail, the notch tail promotes transcription of notch target genes
if there is transcription of notch target genes, is delta activated or repressed in this cell
repressed - but you might have some if the proteins made were repressors
does the cell with active notch target genes differentiate or not differentiate
not differentiate
how do notch small fragments free up in the ec space
through cleavage
state the 4 types of mechanisms that hedgehog signaling combines
- GPCRs, cAMP, PKA
- proteolysis
- cytoskeleton - mediated transport
- paracrine signaling
describe the actions when hedgehog signaling is present
- Hedgehog binds and inactivates Patched
- Smoothened is active and moves to the tip of the primary cilium
- Gpr161 and PKA are inactive
- Gil3 is not proteolytically processed so it
does not inhibit hedgehog target genes - SuFu and Gli2 move along microtubules to
the tip of the primary cilium - Smoothened releases Gli2 from SuFu
- Gli2 moves along microtubules from primary cilium to nucleus
- Gli2 activates hedgehog target genes
describe the sequence of events when there is no hedgehog signal
- Patched is active in the cilium
- Active Patched inhibits Smoothened and
keeps Smoothened out of the primary cilium - SuFu binds and inhibits Gli2 & Gli3
- GPCR (Gpr161) is active
- Active Gpr161 promotes cAMP synthesis
- cAMP activates PKA
- PKA phosphorylates Gli3
- Gli3 phosphorylation causes Gli3 proteolytic processing
- The remaining fragment of Gli3 moves to the nucleus to repress expression of hedgehog target genes
what processes are the following involved in
1. notch (3)
2. hedgehog (Shh) (5)
- tissue patterning, neurogenesis, stem cell renewal
- neural tube closure, tissue patterning, limb development, lung development, stem cell renewal
Which of the following terms best describes Sevenless signaling?
a) Contact dependent signaling
b) Paracrine signaling
c) Two-component signaling
d) Receptor threonine/serine kinase signaling
A
