Flashcards in 26_Signal Transduction IV Deck (28)
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1
What is an example of a cytoplasmic protein-tyrosine kinase?
Jak
2
In (ligand/receptor)-mediated dimerization, each RTK chain binds a distinct ligand, while in (ligand/receptor)-mediated dimerization, a single ligand binds to two binding sites
receptor-mediated
ligand-mediated
3
How do RTKs phosphorylate?
trans-autophosphorylation
(each chain possesses a kinase domain; once dimerized, these domains cross-phosphorylate)
4
The tyrosine kinase domain is on the (extracellular/cytoplasmic) side of an RTK.
cytoplasmic
5
Contrast the extracellular side of EGF receptors, insulin receptors, and PDGF receptors.
- Insulin receptor dimers are connected by disulfide bridges.
- EGF receptors have cysteine-rich domains outside the cell
- PDGF receptors have Ig-like domains.
- Insulin receptors are composed of two subunits (a and b).
6
Where are the a and b subunits of the insulin receptor located? How are they joined?
a subunits are entirely extracellular, while b subunits are transmembrane.
They are connected via disulfide bridges.
7
What is the function of autophosphorylation sites on RTKs?
- regulate kinase activity (increase)
- docking sites for signalling molecules
8
What are the two domains that can bind phosphorylated tyrosines?
SH2 (Src homology domain 2)
PTB (phosphotyrosine-binding domain)
9
What do SH3 domains bind?
hydrophobic proline residues
10
Grb2 is an example of a (adaptor protein/docking protein/TF/signalling enzyme).
adaptor protein
11
Grb2 interacts with the RTK via its _____ domain.
SH2
12
Which is a docking protein?
Grb2, Sos, Jun, IRS, Shp2, PI3K, PLC
IRS
13
Shp2 is a (phosphatase/kinase).
phosphatase
14
IRS interacts with an RTK via its ____ domain.
PTB
15
Which accessory protein activates G-proteins? How does it function?
GEF (guanine-nucleotide exchange factor): stimulates exchange of GDP for GTP
16
How do GAPs modulate G-protein activity?
GAP = GTPase-activating protein
inactivates by stimulating hydrolysis of GTP to GDP
17
Which accessory protein inhibits release of GDP?
GDIs (guanine nucleotide-dissociation inhibitors)
18
Mutations in human Ras prevent _________ and mutant Ras remains in the (ON/OFF) position.
GTP hydrolysis
ON
19
IRS is a docking protein that helps recruit both a kinase and a phosphatase. What are they?
kinase: PI3K
phosphatase: Shp2
20
What domain do signalling enzymes use to dock to RTKs?
SH2
21
What is the effector of Ras in the MAP kinase cascade?
Raf kinase
22
What is the adaptor protein in the MAP kinase cascade?
Grb2
23
What is the role of Sos in the MAP kinase cascade?
GEF
24
What is the final protein to be phosphorylated in the MAPK cascade?
a TF
(e.g. Fos & Jun)
25
How does phosphorylation affect the location of Raf?
Inactive Raf is soluble; once phosphorylated, it becomes membrane-bound.
26
What is the significance of MKP-1 transcription in the MAPK cascade?
MKP-1 is a MAPK phosphatase. It will act as a phosphatase and will inactivate ERK, thereby turning the cascade OFF.
27
How does PKA affect Raf?
It phosphorylates Raf, thereby inactivating it.
28