Principles of Cell Signaling Flashcards
1
Q
what do signaling cells produce
A
an extracellular signal molecule which is detected by a target cell
2
Q
what do target cells do in cell signal transduction
A
- recognize and respond to extracellular signal molecules via receptors that are specific to signal molecules
- target cell converts the extracellular signal to an intracellular signaling molecule to alter cell behaviour
3
Q
what are the 4 methods of cell signal transduction
A
- endocrine signal transmitted throughout entire system via bloodstream
- paracrine signals transmitted locally in extracellular fluid
- neuronal signal transmitted to a specific target
- contact-dependent signal transmitted to cells in direct contact
4
Q
what is autocrine signaling
A
cells responding to local mediators that they produce themselves
5
Q
where are large hydrophilic signals recognized
A
plasma membrane
6
Q
where are small hydrophobic signals recognized
A
cytosol
7
Q
signal reception is limited and controlled how
A
through the expression of receptors
8
Q
do cells depend on extracellular signals
A
yes, multiple
9
Q
absence or inhibition of appropriate signals leads to what
A
cell death (apoptosis)
10
Q
can signals modify effects of each other
A
yes (allows them to finely tune the cells response)
11
Q
can extracellular signals elicit responses at diff speeds
A
yes
12
Q
what speeds can extracellular signals elicit responses at
A
- fast response change in protein activity already present in the cell
- slow response change in gene expression and protein synthesis
13
Q
where are most extracellular signal molecules recognized
A
plasma membrane
14
Q
how is a response to an extracellular signal recognized at the plasma membrane generated
A
the activation of an effector protein
15
Q
what functions to intracellular signaling pathways perform
A
- relay aid in spread through the cell
- amplify make the signal stronger
- integrate limit relay until there are multiple signals
- distribute relay signals to multiple effectors
- engage in feedback alter response by regulating components upstream in signaling pathway
16
Q
what are the two kinds of feedback
A
- positive downstream components enhances initial signal (all or nothing)
- negative downstream components inhibits initial signal (oscillating)
17
Q
where can feedback occur
A
anywhere in the signaling pathway
18
Q
what does it mean for a protein to behave as molecular switches
A
once they receive a signal they switch to an active or inactive state
19
Q
what are two kinds of protein switches
A
- phosphorylation phosphate group is bound or cleaved, changing activation
- GTP-binding active when bound to GTP and inactive when bound to GDP
20
Q
what do kinases do
A
transfer a phosphate group to a molecule
21
Q
what do protein kinases do
A
transfer terminal phosphate from ATP to a serine, theronine, or tyrosine side chain
22
Q
what are the 2 main types of GTP-binding proteins
A
- monomeric GTPases controlled by regulatory proteins (GEF and GAP)
- G proteins large, trimeric, relay messages from G-protein coupled receptors
23
Q
what does GEF stand for
A
guanine nucleotide exchange factor (a regulatory protein for monomeric GTPases)
24
Q
what does GAP stand for
A
GTPase-activating protein (a regulatory protein for monomeric GTPases)
25
what do cell-surface receptors do
bind to an extracellular signals and transduce its message into one or more intracellular signaling molecules
26
what are the primary classes of cell-surface receptors
- ion-channel-coupled
- G-protein-coupled
- enzyme-coupled
27
how many receptors are there for extracellular signaling molecules
more than one type
28
what do ion-channel-coupled receptors do
- change the permeability of the plasma membrane to selected ions
- alter membrane potential
- sometimes produce an action potential
29
what do G-protein-coupled receptors do
- activate membrane-bound GTP-binding proteins
- activate or inhibit an enzyme/ ion channel in the plasma membrane to trigger an intracellular signaling cascade
30
what do enzyme-coupled receptors do
- act an enzymes or associate w enzymes inside the cell
- activate a wide variety of intracellular signaling pathways
31
what are the largest family of surface receptors
G-protein-coupled receptors (GPCRs)
32
describe the structure of GPCRs
single polypeptide chain that traverses the plasma membrane 7 times
33
what GPCRs do
- involved in many cell processes
- mediate responses to a diverse range of extracellular signals
34
describe the structure of G proteins
- composed of 3 protein subunits: alpha, beta, gamma
- alpha and gamma subunits are tethered to membrane via covalently linked lipids
35
what happens when an extracellular signal binds to a GPCR
- receptor activates a G protein on the cytosolic side of the membrane
- this alters the affinity of the alpha subunit for GDP
- GDP is exchanged for GTP
- this may separate the G protein into 2 activated parts: alpha subunit, beta/gamma subunit
- the effector is now activated!!!
- eventually alpha subunit will hydrolyze bound GTP to GDP
- G protein now returns in inactive conformation
36
active time of the G protein components is determined by what
the behaviour of the alpha subunit
37
how can the bound GTP being hydrolyzed tto GDP be accelerated
by a regulator of G-protein signaling (RGS) protein
38
G proteins directly regulate the activity of what
ion channels
39
how do G proteins slow heart rate
- nerve signals to slow heart rate release acetylcholine
- acetylcholine bind to GPCR
- this activates the G protein
- the beta/gamma complex binds to the intracellular face of a K+ channel, forcing it open
40
what does adenylyl cyclase do
produces cyclic AMP
41
what does phospholipase C do
produces inositol triphosphate and diacylglycerol
42
what are 2 most frequent taregts when activating membrane-bound enzymes
- adenylyl cyclase
- phospholipase C
43
how does the cyclic AMP pathway work
- activated G protein alpha subunit switches on adenylyl cyclase
- this increases the synthesis of cAMP from ATP
- cyclic AMP phosphodiesterase coverts cAMP into AMP, terminating the signal
- cyclic AMP phosphodiesterase is always active inside the cell to make this signal termination quick
44
how does cAMP exert most of its effects
- **by activating cyclic-AMP-dependent protein kinase (PKA)**
- this phosphorylates specific target proteins which vary depending on cell type
45
what kinase is active in cAMP signaling- enzyme activation
PKA
46
what kinase is active in cAMP signaling- gene transcription
PKA
47
what kinase is active in the inositol phospholipid pathway
- inositol 1.4.5-triphosphate (IP3)
- diacylglycerol (DAG)
48
what is the largest class of enzyme-coupled receptors
receptor tyrosisne kinases (RTKs)
49
how do receptor tyrosisne kinases (RTKs) work
cytosolic domain phosphorylates tyrosines on intracellular signaling proteins
50
what are enzyme coupled receptors
receptors that form a complex w another protein, which acts an enzyme or the cytosolic domain of the receptor itself acts as an enzyme
51
in many cases, binding of an extracellular signal causes two receptors to form a _____, which does what
- dimer
- where each receptor tail phosphorylates the other activating the kinase domains
52
what happens in active RTKs
the newly phosphorylated tyrosines serve as docking sites for intracellular signaling proteins
53
what are some of the roles of intracellular signaling proteins that dock on active RTKS
- some only as scaffolds
- others are activated upon binding to aid in the propogation of the signal
54
how long are RTK signal complexes active for
until it is dissociated by tyorsine phosphatases or the complex is degraded via endocytosis
55
RTKs recruit and activate what
- many kinds of intracellular signaling proteins
- including the monomeric GTPase **Ras**
56
what is Ras
- resembles and functions in a similar manner to the alpha subunits in trimeric G proteins
- activate when bound to GTP
- inactive when bound to GDP
57
describe Ras in its active state
- *when bound to GTP*
- it initiates phosphorylation cascades to transmit a signal from the plasma membrane to the nucleus
58
describe RTK-mediated signal transmission from the plasma membrane to the nucleus
- includes a 3-kinase module named MAP-kinase signaling module
- this is named after the final enzyme in the sequence (MAP- kinase)
59
what does MAP kinase do
- phosphorylates various proteins including transcription regulators
- may stimulate proliferation, survival, or induce differentiation
60
RTKs can promote cell growth how
by activating phosphoinositide 4-kinase (PI 3-kinase)
61
what do PI 3-kinase do
phosphorylated inositol phospholipids in the plasma membrane to serve as docking sites for intracellular signaling proteins (including Akt)
62
what kinases are present in PI-3-Kinase-Akt signaling pathway
- PI 3-kinase
- Akt (aka PKB)
63
what does Akt do
- promotes survival often through the inhibition of signaling proteins
- promotes cell growth through the activation of signaling proteins
64
how does Akt promote survival
phosphorylates and inactivates the cytosolic signaling protein Bas, which activates apoptosis
65
how does Akt promote cell growth
indirectly activates a large serine/threonin kinase, Tor, that stimulates protein synthesis and inhibits protein degredation
66
what allows for finely tunes responses to a combination of signals
integrating the information from a high volume of messages for an appropriate response
67
