Unit 7 Flashcards
"Principles of Cell Signalling"
//Cells communicate by means of
extracellular signaling molecules
Signaling molecules are synthesized and released by
signaling cells
Signaling molecules are synthesized and released by signaling cells and produce
a specific response only in target cells that have receptors for the signaling molecules.
Signal transduction:
the process of converting an extracellular signal (signaling molecule A) into an intracellular signal (signaling molecule
B) in a target cell.
The intracellular signal initiates a series of intracellular reactions that regulate (6):
(1) Transcription
(2) Survival
(3) Protein synthesis
(4) Movement
(5) Cell death
(6) Metabolic changes
What are the six steps in signalling:
- SYNTHESIS of the signaling molecule by the signaling cell
- RELEASE of the signaling molecule by the signaling cell
3.TRANSPORT of the signaling molecule to the target cell - DETECTION of the signal by a specific receptor protein
- a CHANGE in cellular metabolism, function, or development triggered by the receptor-signaling molecule complex
- REMOVAL of the signaling molecule ,which terminates the cellular response
Signaling can be classified into 4 types that act over short or long distances:
- Autocrine
- Paracrine
- Endocrine
- Contact-dependent
In autocrine signaling (1/4 types signalling), cells respond to
signaling molecules that they themselves release.
This type of signaling is particularly common in cancer cells, which overproduce and release growth factors that stimulate inappropriate, unregulated growth and division of themselves, leading to cancer development
autocrine signaling
In paracrine signaling (1/4 types of signaling) …
the signaling molecules released by a signaling cell into the extracellular medium act LOCALLY to affect target cells in CLOSE PROXIMITY to the signaling cell
In endocrine signalling (1/4 types of signalling) , the signalling molecules are called __ and act on __
in endocrine signalling, the signalling molecules are called HORMONES and act on target cells DISTANT from their site of synthesis by endocrine cells
Hormones produced in endocrine cells are secreted into__ and can be __
Hormones produced in endocrine cells are secreted into the bloodstream and can be distributed widely throughout the body.
In contact-dependent signaling (1/4 types of signalling), a ___ in the plasma membrane of the signaling cell binds to a receptor molecule embedded in the plasma membrane of the target cell.
membrane-anchored signal
In contact-dependent signaling, a membrane-anchored signal __
in the plasma membrane of the signaling cell binds to a receptor molecule embedded in the plasma membrane of the target cell.
In contact-dependent signaling, a membrane-anchored signal in the plasma membrane of the signaling cell binds to a receptor molecule embedded in the plasma membrane of the target cell. This requires __
cells to be in direct membrane-to-membrane contact with each other
contact dependant signaling does not require:
the release of a signaling molecule.
What type of signalling does not require the release of a signalling molecule?
contact dependant signalling
true/false: in extracellular signalling, the signalling molecule is the signal?
The extracellular signaling molecule alone is not the signal. The signal depends on how the target cell interprets the signaling molecule, which is dictated by intracellular signaling pathways.
signal is the “process”
in extracellular signalling, the signalling molecule alone is not the signal. The signal depends on:
how the target cell interprets the signaling molecule, which is dictated by intracellular signaling pathways.
Intracellular signaling pathways: Signaling pathways consist of
a series of proteins and/or second messengers.
Intracellular signaling pathways:Each protein in a pathway
alters the conformation or activity of the next
protein.
Intracellular Signaling Pathways: In some cases the intracellular signaling molecule can be __ . These are referred to as ___.
In some cases the intracellular signaling molecule can be a small molecule (e.g. cAMP, Ca2+). These are referred to as second messengers.
in intracellular signaling pathways: protein conformation is usually altered by:
phosphorylation
in regards to intracellular signaling pathways (more specifically,protein conformation), kinases do what?
add phosphate
in regards to intracellular signaling pathways (more specifically,protein conformation), phosphotases do what?
remove a phosphate
Intracellular signaling pathways: Target proteins ultimately __
receive a message to alter cell activity.
When signaling is mediated by __, upon activation of the signaling cascade there are __ types of molecular switches:
When signaling is mediated by proteins, upon activation of the signaling cascade there are four types of molecular switches
When signaling is mediated by proteins, upon activation of the signaling cascade there are four types of molecular switches:
- phosphorylation-dephosphorylation
- GTP binding (e.g. G-protein-coupled receptor)
- assembly-disassembly of protein complexes
- proteolysis (irreversible)
Protein phosphorylation can __
change protein behaviour in different ways
Molecular switch 1/4: phosphorylation-dephosphorylation: Protein phosphorylation can change protein behaviour in different ways (4):
- It can activate or inactivate an enzyme.
- It can promote or interfere with protein-protein interactions.
- It can change the subcellular location of the protein.
- It can trigger protein degradation
a kinase tends to __ a signal
activate
a phosphatase tends to __ a signal.
inactivate
A GTP-binding protein is active when bound to __
GTP
A GTP-binding protein is inactive when bound to __
GDP
In the absence of a signal, the GTP-binding protein is bound to
GDP
A GTP-binding protein is active when bound to GTP and inactive when bound to GDP.
In the absence of a signal, the GTP-binding protein is bound to GDP.Signals activate the release of __ and the subsequent binding to ___
Signals activate the release of GDP and the subsequent binding to GTP
how do intracellular signaling proteins convert active form of GTP to GDP?
The GTPase activity of these intracellular signaling proteins hydrolyses the bound GTP to GDP and Pi, thus converting the active form back to the inactive form
Many signal-transduction cascades contain:
multiprotein signaling complexes.
Some proteins act as __ to bring other signaling molecules into proximity for sequential activation
scaffolds
Some signaling proteins can interact with the activated receptor and
transmit the signal to downstream effector proteins
Most interactions during signaling are mediated by specific _
protein domains
Define protein domain:
stretches of amino acids that share some degree of similarity and can function
independently of the entire protein.
Some examples of protein interaction domains found in signaling molecules are (4):
(1) Src homology 2 (SH2) domains
(2) Src homology 3 (SH3) domains
(3) pleckstrin homology (PH) domains (4) phosphotyrosine-binding (PTB) domains
Some signaling cascades are mediated by proteolysis where:
the intracellular portion of the receptor is cleaved and acts as a signaling molecule.
Some signaling cascades are mediated by ___ where the intracellular portion of the receptor is cleaved and acts as a signaling molecule.
proteolysis
SH2 domain –
binds to phosphate in a particular sequence
SH3 domain - binds to
proline-rich sequences
PH domain binds to:
certain phosphoinositides
PTB domain binds to:
phosphorylated tyrosine residues in a particular sequence
In contrast to the other three molecular switches, this type of switch is not reversible:
proteolysis -> once the protein is cleaved it cannot be undone
Molecular switch: phosphorylation can be reversed by a
phosphatase
Molecular switch:GTP activation can be reversed by
GTP hydrolysis
true or false: protein assembly can be undone:
true
Intracellular signaling pathways
The pathway can be thought of as a cascade of events. The cascade serves to (4):
- RELAY THE SIGNAL and help spread it in the cell.
- AMPLIFY THE SIGNAL such that a few extracellular molecules can provoke a large intracellular response.
- INTEGRATE signals from other pathways before relaying them onward.
- DISTRIBUTE THE SIGNAL to a number of different effector proteins evoking a complex response.
Amplification of the epinephrine signal:
1 molecule of epinephrine leads to the production of 100x106 molecules of glucose-1-phosphate
Extracellular signaling molecules fall into __ classes, corresponding to __
Extracellular signaling molecules fall into 2 classes, corresponding to 2 fundamentally different classes of receptors.
1st class (largest) of extracellular signaling molecules:
- extracellular signaling molecules are
too large and too hydrophilic to cross the plasma membrane - receptors are on the outer surface of the plasma membrane of the target cell
2nd class (largest) of extracellular signaling molecules:
-extracellular signaling molecules are sufficiently small and hydrophobic to diffuse across the plasma membrane
-receptors are in the interior of the target cell, either in the cytosol or in the nucleus
Signaling through extracellular signaling molecules:
A receptor protein located on the cell surface receives the extracellular signaling molecule and:
generates a new intracellular signaling molecule in response (protein or second messenger).
Signaling through extracellular signaling molecules: There are 3 classes of ligand-triggered cell-surface receptors:
- G-protein-coupled receptors – found in virtually all cells
- Ion-channel-coupled receptors – especially important in neuronal signaling
- Enzyme-coupled receptors
class of ligand-triggered cell-surface receptors found in virtually all cells
G-protein -coupled receptors
class of ligand-triggered cell-surface receptors – especially important in neuronal signaling :
Ion-channel-coupled receptors
Some G proteins stimulate the production of 1,2 diacylglycerol and inositol-1,4,5-triphosphate by
activating phospholipase C and are referred to as
Gq
Some G proteins stimulate the production of cAMP and are referred to a
Gs
Some G proteins stimulate the production of cAMP and are referred to as Gs. Others inhibit the production of cAMP and are called
Gi
The subunits of the heteromeric G protein are called
Gqa for the a subunit and Gqby for the by subunits.
ligand-triggered cell-surface receptors:ion-channel-coupled receptors
Ligand binding changes
the conformation of the ion-channel-linked receptor and opens the channel for ion flow
ligand-triggered cell-surface receptors:An enzyme-coupled receptor ___ switching on an __ of the plasma membrane.
An enzyme-coupled receptor BINDS ITS EXTRACELLULAR LIGAND switching on an ENZYME ACTIVITY ON THE OPPOSITE SIDE of the plasma membrane.
An enzyme-coupled receptor binds its extracellular ligand switching on an enzyme activity on the opposite side of the plasma membrane. The enzyme may be part of (2):
(1) cytoplasmic domain of the receptor
(2)an enzyme that associates with the cytoplasmic domain of the receptor
2nd class of extracellular signaling molecules and receptors: Some extracellular signaling molecules are sufficiently small and
hydrophobic to diffuse across the plasma membrane.
The corresponding receptors are in (2):
the interior of the target cell, either in the cytosol or in the nucleus.
2nd class of extracellular signaling molecules and receptors:Two groups of small, diffusible signaling molecules:
- Hormones
- Nitric oxide (NO)
group of small, diffusible signaling molecules:
1. Hormones – their receptors are __
transcription factors that regulate expression of specific genes.
group of small, diffusible signaling molecules: 2. Nitric oxide (NO) – Produced by __
the breakdown of arginine
group of small, diffusible signaling molecules: 2. Nitric oxide (NO) – only involved in what kind of signalling
short-lived so only local acting (paracrine signaling),
what group of small diffusable signaling molecules is important in the cardiovascular system:
Nitric oxide (NO)
Cortisol(hormone-example of small diffusable signalling molecule) binds to its receptor in the
cytosol
thyroxine(hormone-example of small diffusable signalling molecule) binds to its receptor in the:
nucleus
Cortisol is produced by
adrenal gland
Cortisol is produced by the adrenal gland under (2):
(1) stress
(2) low blood glucose
cortisol causes the body to (2):
(1) Produce glucose
(2) Suppress the immune system
Describe the 3 steps involved in cortisol binding to its receptor
(1) Cortisol diffuses across the plasma membrane and binds to its receptor protein, which is located in the cytosol.
(2) The binding of cortisol induces a conformational change in the receptor and the complex of cortisol and its receptor are transported into the nucleus through nuclear pores.
(3)In the nucleus, the receptor binds to specific DNA regulatory sequences and induces expression of the downstream genes.
Thyroxine receptor is located in the
nucleus
Thyroxine receptor is located in the nucleus and is bound to DNA either (2):
in the presence or absence of thyroxine.
Thyroxine receptor is located in the nucleus and is bound to DNA either in the presence or absence of thyroxine. In the ABSENCE of thyroxine, the receptor
binds to a REPRESSOR molecule to prevent gene transcription.
Thyroxine is produced by
the thyroid gland
Thyroxine is produced by the thyroid gland and increases:
(1) metabolic rate
(2) protein synthesis
can thyroxine diffuse across the plasma membrane ? if so , how
can diffuse across the plasma membrane where it is transported from the cytosol into the nucleus through NUCLEAR PORES
In the nucleus, binding of thyroxine to its receptor induces
a conformational change such that the receptor now binds to a transcriptional activator, which in turn recruits RNA polymerase. The gene is then transcribed.
a vasodilator, causing the smooth muscle cells lining blood vessels to relax, allowing blood to flow more readily
NO
NO is a vasodilator, causing the smooth muscle cells lining blood vessels to relax, allowing blood to flow more readily. Produced through the action of
acetylcholine.
NO activates ___ , an enzyme that produces __
NO activates guanylyl cyclase, an enzyme that produces cGMP
NO is a vasodilator, causing the smooth muscle cells lining blood vessels to relax, allowing blood to flow more readily. Produced through the action of acetylcholine.
It activates guanylyl cyclase, an enzyme that produces cGMP, cGMP is a second messenger that activates
a protein kinase that phosphorylates specific substrates leading to smooth muscle cell relaxation and vasodilation
therapeutic persepective NO:
Nitroglycerin, used to treat angina (inadequate blood flow to the heart), is converted to NO leading to vasodilation.
Increasing the lifetime of cGMP will increase
blood flow for greater periods of time.
Increasing the lifetime of cGMP will increase blood flow for greater periods of time. Inhibitors of __ (sildenafil, a.k.a. Viagra) achieve this
phosphodiesterase 5
