Cell signaling part 2 Flashcards
1
Q
transmembrane proteins with their ligand-binding domain on the outer surface
A
enzyme-coupled receptors
2
Q
How is ECR different from GPCR differ in terms of cystolic domain?
A
Cystolic domain has intrinsic enzyme activity or associates directly with enzyme
3
Q
Most common type of enzyme-coupled receptors
A
receptor tyrosine kinase
4
Q
How many Human RTKs?
A
60 human RTKs
5
Q
How many structural subfamilies in 60 human RTKs
A
20
6
Q
the binding of the signal protein to the ligand -binding domain on the extracellular side of the receptor
A
activates the tyrosine kinase domain on the cytosolic side
7
Q
Activation of cytoplasmic kinase domains of RTKs
A
dimerization
8
Q
dimerization brings the kinase domains close to each other in an orientation that allows them to phosphorylate each other on specific tyrosines
A
Insulin receptor
9
Q
activate kinase domains
A
Promoting conformational change
10
Q
families of monomeric GTPases
- relay signals from cell-surface receptors
A
Ras superfamily
11
Q
can coordinately spread the signal along several distinct downstream signaling pathways
A
Signaling Hub
12
Q
Three major, closely related Ras proteins in humans
A
H-, K-, and N-ras
13
Q
between two distinct conformational states
A
Molecular switch
14
Q
How does Ras activity acts as molecular switches
A
GTP: on (active)
GDP: off (Inactive)
15
Q
dissociation of GDP; uptake of GTP, activatingRas
A
Ras guanine nucleotide exchange factors (Ras-GEFs)
16
Q
hydrolysis of bound GTP, inactivating Ras
A
Ras GTPase-activating proteins (Ras-GAPs)
17
Q
Are resistant to Ras GAPs
A
Hyperactive mutatant forms of Ras
18
Q
GEF that mediates Ras activation by RTKs
A
Sevenless (Sev)
19
Q
Genetic screens for components of this signaling pathway led to the discovery of a Ras GEF
A
Son-of-sevenless (Sos)
20
Q
which is an adaptor protein that links the Sev receptor to the Sos protein
A
Grb2
21
Q
promotes the Ras activation
A
Sos
22
Q
Short-lived signaling events that is activated by RTKs
A
- Tyrosine phosphorylations and Ras activation
23
Q
relays the signal downstream by phosphorylation
A
MAP kinase
24
Q
Three componens of MAP kinase module
A
- MAPK (Erk)
- MAPKK (Mek)
- MAPKKK (Raf)
25
MAP kinase module
mitogen-activated protein kinase
module
26
MAP Kinase module full name
mitogen-activated protein kinase module
27
enters the nucleus and phosphorylates transcription regulatory complex
erk
28
What does eark activates?
Immediate early genes (Transcription regulators)
29
convey signals from the cell surface to the nucleus and alters the pattern of gene expression
Ras-MAP-kinase signaling pathways
30
mediates different responses in the same cell
MAP kinase modules
31
help prevent cross-talk between parallel MAP kinase modules
Scaffold proteins
32
five parallel MAP kinase modules
- 12 MAP kinases
- 7 MAPKKs
- 7 MAPKKK
33
activated by different kinds of cell stresses (UV, heat shock, osmotic stress)
JNK and p38
34
reduces the opportunities for amplification and spreading of the signal to different parts of the cell
Scaffold strategy
35
the other class of Ras superfamily GTPases that relays signals from cell-surface receptors
Rho Family
36
regulate both the actin and microtubules cytoskeleton controlling cell shape, polarity, motility, and adhesion
Rho family monomeric GTPases
37
Family members of Rho family
Rho, Rac, and Cdc42
38
often bound to guanine nucleotide dissociation inhibitors (GDIs) in the cytosol
inactive Rho family GTPases
39
provides an example of how RTKs can activate a Rho GTPase
ephrin family
40
Ephrins bind and thereby activate members of the
Eph family of RTKs
41
migrating tip of the axon
growth cone
42
activates the Eph receptor
binding of ephrin pritein
43
repelling them from inappropriate regions and keeping them on track
growth cone collapse
44
activate RhoA (Rhoa-GTP)
Rho-GEF ephexin
45
Major changes in the behavior of a cell tend to depend on
Gene expression
46
carry out their effects by initiating signaling pathways that change the activities of transcription regulators
Many extracellular signaling molecules
47
control in gene expression
Less common
48
pathways that depend on ___ ___
regulated proteolysis
49
What does regulated proteolysis control?
control activity
50
What does transcription regulators control?
Location of latent
51
gene expression controlled by
circadian rhythm
52
- used widely in animal development.
- controlling cell face choices and regulating pattern formation and continual renewal of tissues
Notch protein
53
Notch receptor protein is known for its role in?
the production of Drosophila neural cells
54
contact dependent
Lateral inhibition
55
binds to Notch receptor protein
Delta
56
when a precursor cell commits to becoming a ___ cell → signal to its ___ ___ not to do the same
neural
immediate neighbors
57
single-pass transmembrane protein that requires proteolytic processing to function; latent transcription regulator
Notch proteins
58
Binding of ___ → plasma- membrane-bound ___ cleaves
off the cytoplasmic tail of Notch → tail
translocates into the nucleus to
activated the transcription of ___ ___ ___
Delta
protease
Notch response genes
59
tail fragment acts by binding to a ____ ___ → converting from transcriptional repressor into a ___ ___
DNA-binding protein
transcriptional activator
60
Three successive proteolytic cleavage steps of Notch
* 1st – normal biosynthesis
* 2nd – binding of Delta to Notch
* 3rd – cutting free the cytoplasmic tail of the activated receptor
61
final cleavage of the Notch tail
γ-secretase
62
are secreted signal molecules that act as local mediators and morphogens
Wnt proteins
63
Where is Wnt proteins discovered?
Flies and Mice
64
morphogen in wing development
Drosophila - Wingless (Wg) gene
65
promoted the development of breast tumors when activated by the integration of a virus next to it
in mice – Int1 gene
66
latent transcription of regulatory β-catenin
Wnt/β-catenin pathway
67
coordinates the polarization of cells in the plane of a developing of epithelium
planar polarity pathway
68
binds to β-catenin and keeps it out of the nucleus while promoting its degradation
Degradation complex
69
phosphorylates the β-catenin
casein kinase 1 (CK1) and glycogen synthase kinase 3 (GSK3)
70
hold the protein complex together
axin and Adenomatous polyposis coli (APC)
71
is a seven-pass transmembrane protein that resembles GPCRs in structure but does not generally work through the activation of G proteins
Frizzled
72
is a relatively simple single-pass transmembrane protein
LRP (LDL-receptor-related protein)
73
disrupting the β-catenin degradation complex in the cytoplasm
Axin
74
inhibitory complex: LEF1/TCF family bound to a co-repressor protein of the Groucho family
no Wnt signaling
75
coactivator; inducing the transcription of the Wnt target genes
with Wnt signal
76
important regulator of cell growth and prolifereation
Myc
77
Causes development of Colon Cancer
Mutation in APC gene
78
mutation in Apc gene- occure in ___ of human colon cancers
80%
79
How does APC gene causes cancer?
β-catenin accumulates in the nucleus and stimulates the transcription of c-Myc and other Wnt target genes
80
- secreted signal molecules and act as local mediators and morphogens
- Trigger a switch from transcriptional repression to transcriptional activation
Hedgehog proteins
81
Where is hedgehog protein first discovered?
Drosophila
82
What does mutation of hedgehog gene do to drosophila
Produces a larva covered with spiky processes
83
Genes encoding hedgehog proteins
Sonic, Desert, Indian hedgehog
84
Where is hedgehog pathway located
Primary cilium
85
Hedgehog proteins is mediated by a latent transcription regulator called?
Cubitus interruptus (Ci)
86
What if hedgehog signal is absent?
- Ci is ubiquitylated and proteolytically cleaved in proteasomes
87
acts as a transcriptional repressor (in hedgehog proteins)
Ci from smaller fragements
88
processing of Ci protein depends on
- PKA (protein kinase A)
- two kinases (GSK1 and CK1)
89
keep unprocessed Ci out of the nucleus
Scaffold protein Costal2
90
Transmembrane proteins of hedgehog
Patched
iHog
Smoothened
91
Patched keep Smoothened sequestered and inactive
Absence of the signal
92
inhibits the activity of Patched and induces endocytosis and degradation (in hedgehog proteins)
Binding of hedgehog to iHog and Patched
93
recruits protein complex Ci, Fused, and Costal2
Smoothened translocated to the plasma membrane
94
– increase Patched proteins that inhibits further Hedgehog signaling –negative feedback
Genes for patched
95
- latent transcription regulators; stress, inflammatory, and innate immune responses
- excessive signaling found in human cancer
NFkB-Dependent signaling pathway
96
the Drosophila NFkB family member
Dorsal
97
has a crucial role in specifying the dorsal–ventral axis of the developing fly embryo
Dorsal
98
The cell-surface receptors that activate the NFKB signaling pathways in animal cells
- Toll receptors in Drosophila
- Toll-like receptors in vertebrates
99
Toll receptors in Drosophila and Toll-like receptors in vertebrates do?
recognize pathogens and activate this pathway in triggering innate immune responses
100
Proteins in NFkB
RelA, RelB, c-Rel, NFKB1, and NFKB2
101
– inhibitory protein; bind tightly to the dimers and hold them in an inactive state within the cytoplasm of unstimulated cells
IkB
102
activated the gene that encodes IκBa
NFkB
103
negative feedback produces two types of NFκB responses; induce different patterns of gene expression
TNFa(alpha)-induced responses
104
turns on gene A
short exposure to TNF produces single, short pulse of NFκB activation
105
produces oscillation in NFκB activation; turns on both genes
* sustained exposure
106
hydrophobic signal molecules that diffuse directly across the plasma membrane and bind to intracellular receptors (transcription regulators)
nuclear receptor superfamily
107
- bind to specific DNA sequences adjacent to the genes that the ligand regulates
- ligand binding alters the conformation of the receptor protein
Nuclear receptors
108
internal oscillators that control diurnal rhythms
Circadian clocks
109
controls our diurnal cycles of sleeping and waking, body temperature, and hormone release
SCN (Suprachiasmatic nucleus)
110
Process of releasing melatonin
- SCN cells receives signal cues from the retina
- (send information to other brain areas and;) pineal gland
- rest of the body by releasing the hormone melatonin
111
generally depend on negative feedback loops
Circadian clocks
112
coordinate their activities in response to the changing conditions of light, dark, and temperature
Signaling in plants
113
what plants and animals use for signaling
Nitric oxide
cyclic GMP
Ca2+
Rho family GTPases
114
The clylic phosphae that is NOT used by plants
Cyclic AMP
115
cell-surface receptors in plants are
enzyme-coupled
116
Plants rely largely on a great diversity of transmembrane ______ ___
receptor serine/threonine kinases
117
The most abundant types of these receptors have a tandem array of extracellular leucine-rich repeat structures and are therefore
Leucine-rich repeat (LRR) receptor kinases
118
How many LRR receptor kinases in Arabidopsis?
175 LRR receptor kinases
119
Plants synthesize a class of steroids that are called
Brassinosteroids
120
help to coordinate plant development
plant growth regulators (plant hormones)
121
examples of plant hormones
- ethylene
- auxin
- cytokinin
- gibberellins
- abscisic acid
- brassinosteroids
122
are all small molecules made by most plant cells
Growth regulators
123
small gas molecue
Ethylene
124
How does etyhylene influence plant development?
- promote fruit ripening
- leaf abscission
- plant senescence
125
Where are ethylene receptors located?
Endoplasmic reticulum
126
copper-containing ethylene binding domain ; that interacts with a cytoplasmic regions
CTR1
127
CTR1 _____ the ubiquitylation and degradation in proteasomes of nuclear transcription regulator ____
stimulates
EIN3
128
activate the transcription of the large number of ethylene-responsive genes
EIN3
129
- indole-3-acetic acid
- It helps plants grow toward light, grow upward rather than branch out, and grow their roots downward.
Auxin
130
Transport system of Auxin
- Specific plasma memebrane-bound influx transporter proteins
- efflux transporter proteins
131
light- sensitive proteins
- covalently attached light-absorbing chromophore, which changes its shape in response to light and then induces change in the protein’s conformation
Photoproteins
132
red (activates) and far-
red light (inactivates)
Phytochromes
133
phototropism; tendency of plants to grow toward light
Phototropin
134
flavoproteins; sensitive to blue light
cryptochromes
135
blue-light-sensitive enzymes of cryptochromes
Photolyases
136
phototropism; tendency of plants to grow toward light
Phototropin
137
Flavoproteins; sensitive to blue light
Cryptochromes
138
What does cryptochromes do?
- Invovled in repair of ultraviolet-induced DNA damage
139
Importance of cryptochromes in animals
role in circadian clocks
