1
Q
4 steps to cell signalling
A
- signalling molecules released (ligands)
- recognition of signalling molecule by target cell (receptors)
- signal transduction; signalling cascade (conversion of extracellular signal into intracellular instructions)
- final impact on target cell and subsequent impact on organism as whole
2
Q
Cell communication and signal transduction __________ in complexity with multicellular organisms
A
increases
3
Q
modes of signalling
A
- cell to cell
- paracrine (neurotransmitters across a synapse)
- endocrine (hormones)
- autocrine
4
Q
5 classes of ligands
A
- steroid hormones
- eicosanoids
- neurotransmitters
- peptide hormones and polypeptide growth factors
- simple gases
5
Q
steroid hormones
A
- hydrophobic molecules that can diffuse across cell membrane and bind to intracellular receptors
- estrogen, glucocorticoids
6
Q
steroid hormones mode of action
A
endocrine, paracrine, and autocrine
7
Q
eicosanoids
A
-hydrophobic, rapidly broken down that bind to cell surface receptors
8
Q
eicosanoids mode of action
A
paracrine or autocrine
9
Q
neurotransmitters
A
-hydrophilic and bind to cell surface receptors
10
Q
neurotransmitters mode of action
A
endocrine, paracrine, and autocrine
11
Q
peptide hormones and polypeptide growth factors
A
- largest and most variable, primarily hydrophilic and cannot cross cell membrane but bind to cell surface receptors
- insulin, epidermal growth factor
12
Q
peptide hormones and polypeptide growth factors mode of action
A
endocrine, paracrine, and autocrine
13
Q
simple gases
A
-passive diffuse across membrane, bind directly to enzymes and do not use receptors
14
Q
simple gases mode of action
A
paracrine
15
Q
two classes of receptors
A
intracellular and cell surface
16
Q
nuclear receptor superfamily
A
intracellular receptors that primarily function as transcription factors
-glucocorticoids, thyroid hormone
17
Q
3 types of cell surface receptors
A
- g-protein coupled receptors (integral membrane protein)
- receptor protein tyrosine kinases (integral membrane protein)
- cytokine receptor superfamily (peripheral membrane protein)
18
Q
cytokine receptor superfamily function together with..
A
non receptor protein tyrosine kinases
19
Q
glucocorticoid action
A
- inactive when bound to a chaperone
- become active when bound to the ligand
20
Q
dimer
A
two active receptors that translocate to nucleus and associate with co-activator protein HAT
21
Q
active gene transcription
A
glucocorticoid receptor + ligand + HAT coactivator
22
Q
gene regulation by thyroid hormone receptor
A
- receptor (dimer) bound to DNA with or w/o ligand
- w/o ligand receptor binds corepressor HDAC to repress gene transcription
- hormone binds receptor changing conformation to disassociate from HDAC and associate with coactivator HAT allowing gene transcription
23
Q
g-protein coupled receptors
A
largest family of cell surface receptors and are transmembrane proteins with multiple transmembrane domains
24
Q
g-protein
A
transmits G protein coupled receptor signals to intracellular targets via intermediary protein
25
When extracellular receptor domain binds the ligand of g-protein coupled receptors
causes a conformational change activating a G protein. alpha subunit of G protein dissociates from beta and gamma to carry signal to intracellular target
26
adenylyl cyclase
intracellular target molecule
27
tyrosine kinase receptors
- plinked ot intracellular enzymes
- one transmembrane domain
- enzyme activity by intracellular domain of receptor or separate protein associated with intracellular domain
28
how are tyrosine kinase receptors activated
by phosphorylating tyrosine residues on both receptor and target substrates which can then associate with downstream targets and initiate a signalling cascade
29
What proteins can recognize tyrosine kinase receptors?
-insulin and multiple growth factors
30
how do tyrosine kinase receptors change when activated?
dimerization followed by phosphorylation
31
non receptor tyrosine kinase
associate with receptors that contain no catalytic activity
32
intracellular signal transduction
chain of reaction that transmit chemical signals from cell surface to their intracellular targets (signalling cascade)
33
4 pathways of intracellular signal transduction
- 2 indirectly connected ti transcription factors (cAMP and MAP kinase)
- 2 directly coupled to transcription factors (Notch signalling and Wnt pathway)
34
cAMP
cyclic AMP is an important second messenger associated with G protein coupled receptors and is important for response of cells to variety of hormones
35
A phosphate group in cAMP is covalently bound to both the 3’ and 5’ carbon atoms by the enzyme....
adenylyl cyclase
36
second messenger
a compound that is modified as a result of ligand-receptor interaction and relays message from receptor to target
-can be used in multiple pathways
37
adenylyl cyclase
an enzyme that catalyzes formation of cAMP from ATP; stimulated by alpha subunit of activated G protein
38
cAMP phosphodiesterase
an enzyme that degrades cyclic AMP
39
The second messenger _____ initiates intracellular transduction
cAMP
40
regulation of protein kinase A
cAMP binds to cAMP dependent protein kinase called protein kinase A (PKA) causing dissociation of PKA regulatory subunits and it phosphorylates downstream target proteins
41
PKA and CREB
PKA activates transcription factor CREB by phosphorylation; CREB recruits coactivators and initiates transcription at CRE binding sites
42
CRE
specific DNA binding element that is in the promoter region of cAMP responsive genes
43
PKA and glycogen
In regulation of glycogen metabolism, PKA phosphorylates two target enzymes; activates phosphorylase kinase and inhibits glycogen synthase
44
cAMP signaling pathways can effect both...
transcription factors and metabolic enzymes
45
PP1- protein phosphatase 1
counterbalances PKA activity to fine tune the signalling mechanism
46
A single receptor can activate_______ G proteins
multiple
47
1 hormone molecule binding 1 receptor can activate ____ target proteins.
many
48
MAP (mitogen activated protein) kinase
cell surface receptors linked to enzymes to produce intracellular signals
49
MAP kinase pathways can be associated with...
both receptor and nn receptor tyrosine kinases
50
MAP kinases are activated in response to...
a variety of growth factors and other signalling molecules
51
stereotypical MAP kinase pathway
Ras-Raf-MEK-ERK
52
Raf
rapidly accelerating fibrosarcoma; a protein serine/threonine kinase that is activated by Ras and leads to activation of ERK MAP kinase
53
ERK
extracellular signal-regulated kinase
54
MEK
map kinase/ERK kinase; dual specificity protein kinase that activates members of ERK family by phosphorylation of both threonine and tyrosine residues
55
Ras
rat sarcoma; guanine nucleotide-binding proteins that function analogously to alpha subunits of G proteins alternating between inactive GDP-bound and active GTP bound forms; integral membrane lipoprotein
56
___ could be directly linked to growth factor induced cell proliferation
Ras
57
one of the first oncogenes identified in human cancers
Ras
58
GEF
guanine exchange factor; activates Gas
59
mutated Ras
locked in GTP binding form
60
GAP
guanine activating protein; terminates Ras activity
61
intermediate protein
links phosphorylated region of tyrosine kinase with other target molecules
62
notch signalling
example of cell to cell signalling;
- notch receptor receives signal from delta ligand on surface of an adjacent cell
- this activates gamma-secretase enzyme to cleave intracellular domain of notch
- domain translocates to nucleus where it binds and activates transcription factors
63
intracellular domain
vehicle for signal transduction
64
Wnt pathway
Wnt proteins (ligand) is family of secreted growth factors involved in cell fate pathways
- bind to receptors Frizzled and LRP
- Wnt, Frizzled andLRP recruit Dishevelled disrupting the destruction complex of proteins
- this prevents phosphorylation go transcription factor B-Catenin
- once unphosphorylated, is stabilized and can translocate to nucleus
- bind to a repressor and form a complex to activate gene transcription
65
crosstalk
interaction of one signalling pathway with another
66
final impact on cell/organism depends on..
signal pathways intersecting/ crosstalk
BMSC 220
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