Signal transduction process
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About This Presentation
ntroduction
2. Definition
3. Steps Of Signal Transduction
A) Reception
B) Transduction
C) Induction
4. Important component used in Signal Transduction
A) Calcium ion as second messenger
B) Protein Kinase
Types of Signal Transduction
A)...
Slide Content
Signal Transduction
By
KAUSHAL KUMAR SAHU
Assistant Professor (Ad Hoc)
Department of Biotechnology
Govt. Digvijay Autonomous P. G. College
Raj-Nandgaon ( C. G. )
By
KAUSHAL KUMAR SAHU
Assistant Professor (Ad Hoc)
Department of Biotechnology
Govt. Digvijay Autonomous P. G. College
Raj-Nandgaon ( C. G. )
Synopsis
1.Introduction
2. Definition
3. Steps Of Signal Transduction
A) Reception
B) Transduction
C) Induction
4. Important component used in Signal Transduction
A) Calcium ion as second messenger
B) Protein Kinase
1.Introduction
2. Definition
3. Steps Of Signal Transduction
A) Reception
B) Transduction
C) Induction
4. Important component used in Signal Transduction
A) Calcium ion as second messenger
B) Protein Kinase
.
5. Types of Signal Transduction
A) Extra cellular Signal Transduction
B) Intra cellular Signal Transduction
C) Inter cellular Signal Transduction
6. Mechanism of Signal Transduction
A) GPCR pathway
B) RTK pathway
7. Example of Signal Transduction
A) In plants
B) In animals
8. Conclusion
9. Reference…
5. Types of Signal Transduction
A) Extra cellular Signal Transduction
B) Intra cellular Signal Transduction
C) Inter cellular Signal Transduction
6. Mechanism of Signal Transduction
A) GPCR pathway
B) RTK pathway
7. Example of Signal Transduction
A) In plants
B) In animals
8. Conclusion
9. Reference…
Introduction
Cell signaling is a phenomenon in which information
is relayed across the plasma membrane to the cell
interior and often transmitted to the cell nucleus.
Cell signaling includes –
Recognition of the stimulus at the outer surface
of the plasma membrane by a specific receptor
embedded in the membrane.
Transfer of a signal across the plasma
membrane to its cytoplasmic surface.
Cell signaling is a phenomenon in which information
is relayed across the plasma membrane to the cell
interior and often transmitted to the cell nucleus.
Cell signaling includes –
Recognition of the stimulus at the outer surface
of the plasma membrane by a specific receptor
embedded in the membrane.
Transfer of a signal across the plasma
membrane to its cytoplasmic surface.
.
Depending on the type of cell and stimulus, the response
may involve :
a change in gene expression.
an alteration of the activity of metabolic enzymes.
a reconfiguration of the cytoskeleton.
a change in ion permeability.
activation of DNA synthesis.
even the death of the cell.
Cessation of the response as a result of the destruction or
inactivation of the signaling molecules, combined with a
decrease in the level of the extra cellular stimulus.
Depending on the type of cell and stimulus, the response
may involve :
a change in gene expression.
an alteration of the activity of metabolic enzymes.
a reconfiguration of the cytoskeleton.
a change in ion permeability.
activation of DNA synthesis.
even the death of the cell.
Cessation of the response as a result of the destruction or
inactivation of the signaling molecules, combined with a
decrease in the level of the extra cellular stimulus.
2. Definition
Signal Transduction-It is a
series of steps by which
external stimuli are converted
into chemical signals and
then into cellular response.
Biological signal transduction
is a complex process in
which information is passed
along signaling pathways.
Signal Transduction-It is a
series of steps by which
external stimuli are converted
into chemical signals and
then into cellular response.
Biological signal transduction
is a complex process in
which information is passed
along signaling pathways.
.
Ligand–An extra cellular molecule whether organic or
inorganic which binds to receptor and there by alter its
function is called ligand. E.g., ions, sugars, proteins.
Receptor-The protein to which the ligandbinds is
called the receptor.
First messenger –The ligandthat triggered the signal
transduction is first messenger.
Second messenger –A molecule produced in
response to transduction of extra cellular signal is
called second messenger. E.g., Calcium ions, cyclic
AMP.
Ligand–An extra cellular molecule whether organic or
inorganic which binds to receptor and there by alter its
function is called ligand. E.g., ions, sugars, proteins.
Receptor-The protein to which the ligandbinds is
called the receptor.
First messenger –The ligandthat triggered the signal
transduction is first messenger.
Second messenger –A molecule produced in
response to transduction of extra cellular signal is
called second messenger. E.g., Calcium ions, cyclic
AMP.
3. Steps of Signal Transduction
A) Reception-
–Perception of the
environment.
–This could be physical
stimulus or the
introduction of a
hormone.
–The cell targeted by a
particular signal has a
receptor molecule
complementary to the
signal molecule or ligand .
i.e., the ligand fits like a
key in a lock and triggers
a change in the receptor
molecule.
A) Reception-
–Perception of the
environment.
–This could be physical
stimulus or the
introduction of a
hormone.
–The cell targeted by a
particular signal has a
receptor molecule
complementary to the
signal molecule or ligand .
i.e., the ligand fits like a
key in a lock and triggers
a change in the receptor
molecule.
;
B) Transduction–
–Signal transduction converts the change in the receptor to a form that
can bring about a cellular response.
–This might involve a series of steps a signal transduction pathway
that alters and amplifies the change.
–This is the steps in which the first messenger of transduction triggers
the increase of second messenger.
–This stimulus of the first step is increased and transformed into a
chemical form which can then act in the cell.
C) Induction/ Response–
–In the third stage of cell signaling, the transduction processes brings
about a cellular response to the stimulus.
–This response can be any of many different cellular activities, such as
activation of a certain enzymes, re-arrangement of the cytoskeleton ,
activation of specific genes, release of abscissicacid which can
cause stomata to close etc.
B) Transduction–
–Signal transduction converts the change in the receptor to a form that
can bring about a cellular response.
–This might involve a series of steps a signal transduction pathway
that alters and amplifies the change.
–This is the steps in which the first messenger of transduction triggers
the increase of second messenger.
–This stimulus of the first step is increased and transformed into a
chemical form which can then act in the cell.
C) Induction/ Response–
–In the third stage of cell signaling, the transduction processes brings
about a cellular response to the stimulus.
–This response can be any of many different cellular activities, such as
activation of a certain enzymes, re-arrangement of the cytoskeleton ,
activation of specific genes, release of abscissicacid which can
cause stomata to close etc.
Important Component used in the Signal
Transduction:
Ca2+ as second messenger -
–Calcium ion also acts as second messenger in signal transduction
pathways.
–Second messenger is a readily diffusible molecules involved in conveying
information from an extra cellular source to principle target enzyme within
the cell. E.g., IP3, cAMP, cGMP etc.
–In plant Ca2+ act as important signal molecules, which transduces many
signals therefore the concentration of Ca2+ in the cytoplasm must be
maintained.
–The change in the Ca2+ concentration initiates different responses that
vary according to cellular structure. E.g., increase in Ca2+ can initiate
closure of the stomatal aperture in the guard cells.
Protein Kinase–
–Enzyme called protein kinase are important links in many Signal
transduction pathways.
–A protein kinase catalyzes the transfer of phosphate groups from ATP to
another protein.
–One kinase may activate many molecules of the next type of kinase in the
chain, thus amplifying the signal, until the last kinase activates the protein
that carries out final cellular response.
Transduction:
Ca2+ as second messenger -
–Calcium ion also acts as second messenger in signal transduction
pathways.
–Second messenger is a readily diffusible molecules involved in conveying
information from an extra cellular source to principle target enzyme within
the cell. E.g., IP3, cAMP, cGMP etc.
–In plant Ca2+ act as important signal molecules, which transduces many
signals therefore the concentration of Ca2+ in the cytoplasm must be
maintained.
–The change in the Ca2+ concentration initiates different responses that
vary according to cellular structure. E.g., increase in Ca2+ can initiate
closure of the stomatal aperture in the guard cells.
Protein Kinase–
–Enzyme called protein kinase are important links in many Signal
transduction pathways.
–A protein kinase catalyzes the transfer of phosphate groups from ATP to
another protein.
–One kinase may activate many molecules of the next type of kinase in the
chain, thus amplifying the signal, until the last kinase activates the protein
that carries out final cellular response.
5.Types of Signal Transduction
Extra cellular Signal
Transduction
Inter cellular Signal
Transduction
Intra cellular Signal
Transduction
Extra cellular Signal
Transduction
Inter cellular Signal
Transduction
Intra cellular Signal
Transduction
;
A) Extra cellular Signal Transduction -
–Extra cellular signals are those come from out of the network
and that gives some effect to the network via specific interaction
with one of the molecules in the network.
–Most extra cellular chemical signals are water soluble and
membrane impermeable. Example –Steroid hormones.
–Steroid hormones first diffused into the cell membrane and then
bind to their receptor, which are usually located in the cell
nucleus.
–These molecules bind to transmembranereceptor can cause a
structural change in these receptor molecules, which then
induces the production of intracellular signaling molecules.
A) Extra cellular Signal Transduction -
–Extra cellular signals are those come from out of the network
and that gives some effect to the network via specific interaction
with one of the molecules in the network.
–Most extra cellular chemical signals are water soluble and
membrane impermeable. Example –Steroid hormones.
–Steroid hormones first diffused into the cell membrane and then
bind to their receptor, which are usually located in the cell
nucleus.
–These molecules bind to transmembranereceptor can cause a
structural change in these receptor molecules, which then
induces the production of intracellular signaling molecules.
;
B) Inter cellular Signal Transduction–
This type of signal transduction describes the mechanism by
which one cell (sender cell) send a message to change the
function of another cell (target cell).
Two cells can communicate by two methods –
Contact dependent signaling –This type of signaling
requires direct physical contacts between sender cell and
target cell.
The second method involved release of secreted
molecules from the sender cell to the target cell and does
not requires direct contact between the sender cell and
target cell .
B) Inter cellular Signal Transduction–
This type of signal transduction describes the mechanism by
which one cell (sender cell) send a message to change the
function of another cell (target cell).
Two cells can communicate by two methods –
Contact dependent signaling –This type of signaling
requires direct physical contacts between sender cell and
target cell.
The second method involved release of secreted
molecules from the sender cell to the target cell and does
not requires direct contact between the sender cell and
target cell .
C) Intra cellular Signal Transduction -
Intra cellular signal transduction is largely carried out by second
messenger molecules . Intracellular signaling molecules in
eukaryotic cell includes . , heterotrimeric G-protein small GTPase,
cyclic nucleotide , such as cAMP , cGMP and Ca2+ ion.
The intracellular signaling usually ideas to certain cellular
responses such as chemotaxis , morphological changes , the
modulation of signal transduction pathway , the regulation of gene
expression , growth and cell division cycle etc.
Intra cellular signal transduction is largely carried out by second
messenger molecules . Intracellular signaling molecules in
eukaryotic cell includes . , heterotrimeric G-protein small GTPase,
cyclic nucleotide , such as cAMP , cGMP and Ca2+ ion.
The intracellular signaling usually ideas to certain cellular
responses such as chemotaxis , morphological changes , the
modulation of signal transduction pathway , the regulation of gene
expression , growth and cell division cycle etc.
a) Cyclic AMP–
Cyclic AMP is a second messenger, a substance that is released into the interior
of the cell following the binding of a first messenger –a hormone or other ligand
–to a receptor at the outer surface of the cell.
Cyclic AMP is only one of a number of substances that act as second-
messengers in eukaryotic cells.
Cyclic AMP is synthesized by an integral membrane protein called adenylyl
cyclase, whose catalytic resides at the inner surface of the plasma membrane.
The cellular response by synthesizing cAMP, adenylyl cyclase is an effector.
cAMP evokes a response that leads to glucose mobilization by initiating a chain
of reactions.
The first step in this reaction cascade occurs as the hormone binds to its
receptor, activating its adenylyl cyclase effector, which catalyzes the formation of
cAMP .
Cyclic AMP is a second messenger, a substance that is released into the interior
of the cell following the binding of a first messenger –a hormone or other ligand
–to a receptor at the outer surface of the cell.
Cyclic AMP is only one of a number of substances that act as second-
messengers in eukaryotic cells.
Cyclic AMP is synthesized by an integral membrane protein called adenylyl
cyclase, whose catalytic resides at the inner surface of the plasma membrane.
The cellular response by synthesizing cAMP, adenylyl cyclase is an effector.
cAMP evokes a response that leads to glucose mobilization by initiating a chain
of reactions.
The first step in this reaction cascade occurs as the hormone binds to its
receptor, activating its adenylyl cyclase effector, which catalyzes the formation of
cAMP .
b) Cyclic GMP–
Cyclic guanine monophosphateis known as CylicGMP.
CylicGMP is synthesized by guanylcyclasefrom GTP.
In plant cell CylicGMP may participate in transducingsignals of fungal
invation, Red light signals mediated by phytochrome.
The tomato aureamutant, which lack Phy-a has been used to demonstrate
the involvement of cGMPin phytochrometransduction.
Individual etiolated cells injected with cloned and reconstituted phytochrome
become sensitive to Red light.
The transformed cell can then form chloroplast when reradiated with red
light.
Injection of calcium ion alone induced partial chloroplast formation.
Complete differentiation of chloroplast required concomitant injections of
cyclic GMP on it own induced anthocyaninformation.
Cyclic guanine monophosphateis known as CylicGMP.
CylicGMP is synthesized by guanylcyclasefrom GTP.
In plant cell CylicGMP may participate in transducingsignals of fungal
invation, Red light signals mediated by phytochrome.
The tomato aureamutant, which lack Phy-a has been used to demonstrate
the involvement of cGMPin phytochrometransduction.
Individual etiolated cells injected with cloned and reconstituted phytochrome
become sensitive to Red light.
The transformed cell can then form chloroplast when reradiated with red
light.
Injection of calcium ion alone induced partial chloroplast formation.
Complete differentiation of chloroplast required concomitant injections of
cyclic GMP on it own induced anthocyaninformation.
c) Calcium Signals–
Calcium is the principle element in signal transduction.
Cytosolic calcium occupies a pivotal in plant cell signal transduction.
The plant signals to be transduced through (Ca2+) include to cell, wind,
temperature, wounding, oxidative stress, Red light, osmotic stress and
mineral nutrition etc.
Ca2+ signaling depend on the concentration of Ca2+ across the plasma
membrane and intra cellular membrane.
Cell maintain very low concentration of cytosolic Ca2+ to facilitate signaling
process.
The vacuole and rough endoplasmic reticulum constitute large intercellular
store of Ca2+ which can be mobilized by IP3 and other signals synthesized
by the plasma membrane.
Calcium is the principle element in signal transduction.
Cytosolic calcium occupies a pivotal in plant cell signal transduction.
The plant signals to be transduced through (Ca2+) include to cell, wind,
temperature, wounding, oxidative stress, Red light, osmotic stress and
mineral nutrition etc.
Ca2+ signaling depend on the concentration of Ca2+ across the plasma
membrane and intra cellular membrane.
Cell maintain very low concentration of cytosolic Ca2+ to facilitate signaling
process.
The vacuole and rough endoplasmic reticulum constitute large intercellular
store of Ca2+ which can be mobilized by IP3 and other signals synthesized
by the plasma membrane.
6. Mechanism (Pathway) of Signal Transduction :
A)GPCR pathway ( G-protein coupled receptor ) -
G-proteins were discovered and characterized by Martin Redbelland
his Colleagues at the National Institute of health in the early 1970s.
Many extra cellular stimuli (first messengers) initiate responses by
interacting with G-protein coupled receptors (GPCR) on the outer cell
surface and stimulating the release of a second messenger within the
cell.
Many extra cellular messenger molecules act as binding to receptors
that are integral membrane proteins containing seven membrane
spanning α helices (GPCRs).
The signal is transmitted from the receptor to the effectorby a
heterotrimericG-protein.
These proteins are referred to as heterotrimericbecause they have
three subunits (α, β and γ) and as G proteins because they bind
guanines either GDP or GTP.
A)GPCR pathway ( G-protein coupled receptor ) -
G-proteins were discovered and characterized by Martin Redbelland
his Colleagues at the National Institute of health in the early 1970s.
Many extra cellular stimuli (first messengers) initiate responses by
interacting with G-protein coupled receptors (GPCR) on the outer cell
surface and stimulating the release of a second messenger within the
cell.
Many extra cellular messenger molecules act as binding to receptors
that are integral membrane proteins containing seven membrane
spanning α helices (GPCRs).
The signal is transmitted from the receptor to the effectorby a
heterotrimericG-protein.
These proteins are referred to as heterotrimericbecause they have
three subunits (α, β and γ) and as G proteins because they bind
guanines either GDP or GTP.
Action of G-protein coupled receptor
Mechanism of G –protein coupled receptors involves following steps :
–When a ligandbinds to a G -protein coupled receptor, it induces a
conformational changes of the receptor that increases the affinity of
the corresponding G –protein.
–The ligandbound receptor binds to the G –protein on the inner
surface of the membrane, forming a receptor G-protein complex.
–Interaction with the receptor induces a conformational change in the α
subunit that causes the subunit to release its bound GDP and bind a
GTP replacement .
–While in the activated state, a single receptor can activate a
succession of G –protein molecules, providing the first amplification
step in the pathway.
–The exchange of GDP by GTP alters the conformational of the Gα
subunit, causing it to dissociate from the receptor and from the other
two subunits of the G –protein, which remain together as a G βγ
complex.
–When a ligandbinds to a G -protein coupled receptor, it induces a
conformational changes of the receptor that increases the affinity of
the corresponding G –protein.
–The ligandbound receptor binds to the G –protein on the inner
surface of the membrane, forming a receptor G-protein complex.
–Interaction with the receptor induces a conformational change in the α
subunit that causes the subunit to release its bound GDP and bind a
GTP replacement .
–While in the activated state, a single receptor can activate a
succession of G –protein molecules, providing the first amplification
step in the pathway.
–The exchange of GDP by GTP alters the conformational of the Gα
subunit, causing it to dissociate from the receptor and from the other
two subunits of the G –protein, which remain together as a G βγ
complex.
–Each dissociated Gα subunit (with GTP attached) is free to
activate the effector molecule, such as adenylyl cyclase,
which puts the second messenger system into operation.
–In this case, activation of the effector leads to the production
of cyclic AMP molecules.
–The G βγ subunit complex may bind its own downstream
effectors i.e., providing an additional pathway for
transmission of signals in a target cell.
–Binding of a ligand to a GPCR has generated to activated
signaling proteins –
A ligand bound GPCR, which acts on G –proteins.
Free GTP bound Gα subunits, which act on effector.
activate the effector molecule, such as adenylyl cyclase,
which puts the second messenger system into operation.
–In this case, activation of the effector leads to the production
of cyclic AMP molecules.
–The G βγ subunit complex may bind its own downstream
effectors i.e., providing an additional pathway for
transmission of signals in a target cell.
–Binding of a ligand to a GPCR has generated to activated
signaling proteins –
A ligand bound GPCR, which acts on G –proteins.
Free GTP bound Gα subunits, which act on effector.
B) RTK pathway ( Receptor Tyrosine kinase)–
Receptor Tyrosine kinaseis a second major type of signaling pathway.
A wide variety of extra cellular agents interact with RTKs on the surfaces
of target cells to regulate such diverse processes as cell growth and
proliferation, cell differentiation, phagocytosis, cell motility, and cell
survival.
Among of these agents are hormones, such as insulin and growth
hormones and growth factors such as epidermal growth factor (EGF) etc.
RTKs receptors are present as monomer in an unstimulatedcell.
After a binding of the ligandleads to dimerizationof the receptor and
activation of its kinaseactivity causing it to add phosphate groups to the
cytoplasmicdomain of the receptor.
The newly formed phosphotyrosineresidues of the receptor serve as
binding sites for target proteins containing SH 2 domains, which become
activated as a result of their interaction with the receptor.
RasMAP kinasepathway is the best channelized signaling cascade that
is termed by an activated proteintyrosinekinase.
Receptor Tyrosine kinaseis a second major type of signaling pathway.
A wide variety of extra cellular agents interact with RTKs on the surfaces
of target cells to regulate such diverse processes as cell growth and
proliferation, cell differentiation, phagocytosis, cell motility, and cell
survival.
Among of these agents are hormones, such as insulin and growth
hormones and growth factors such as epidermal growth factor (EGF) etc.
RTKs receptors are present as monomer in an unstimulatedcell.
After a binding of the ligandleads to dimerizationof the receptor and
activation of its kinaseactivity causing it to add phosphate groups to the
cytoplasmicdomain of the receptor.
The newly formed phosphotyrosineresidues of the receptor serve as
binding sites for target proteins containing SH 2 domains, which become
activated as a result of their interaction with the receptor.
RasMAP kinasepathway is the best channelized signaling cascade that
is termed by an activated proteintyrosinekinase.
Map Kinase pathway
7. Examples of Signal Transduction
A) In plants–
The role of Calcium as an
intracellular messenger in guard cell
closure .
Abscisic acid (ABA) controls the
stomatal pores size.
When ABA levels rise, calcium ion
channels in the plasma membrane
are opened, allowing the influx of
Ca2+ from internal stores.
The subsequent elevation of
intracellular (Ca2+) closes K+ influx
channels and opens K+ efflux
channels, leading a drop in internal
solute concentration and osmotic
loss of water.
A) In plants–
The role of Calcium as an
intracellular messenger in guard cell
closure .
Abscisic acid (ABA) controls the
stomatal pores size.
When ABA levels rise, calcium ion
channels in the plasma membrane
are opened, allowing the influx of
Ca2+ from internal stores.
The subsequent elevation of
intracellular (Ca2+) closes K+ influx
channels and opens K+ efflux
channels, leading a drop in internal
solute concentration and osmotic
loss of water.
‘
B) In Animals–
Calcium induced Calcium
released.
It occurs in excitable cells, such as
cardiac muscles.
A change in membrane voltage
causes the opening of voltage –
gated calcium channels in the
plasma membrane, allowing entry
of a small amount of Ca2+.
The calcium ions bind to the
ryanodinereceptor in the SER
membrane.
Leading to the release of stored
Ca2+.
The calcium ions are subsequently
removed from the cytosolby the
action of the Ca2+ pump located in
the membrane of the SER.
B) In Animals–
Calcium induced Calcium
released.
It occurs in excitable cells, such as
cardiac muscles.
A change in membrane voltage
causes the opening of voltage –
gated calcium channels in the
plasma membrane, allowing entry
of a small amount of Ca2+.
The calcium ions bind to the
ryanodinereceptor in the SER
membrane.
Leading to the release of stored
Ca2+.
The calcium ions are subsequently
removed from the cytosolby the
action of the Ca2+ pump located in
the membrane of the SER.
8. Conclusion
Cell signaling can affect virtually every aspect of cell
structure and function. An understanding of the cell signaling
requires knowledge about other types of cellular activity. Cell
signaling is also intimately involved in the regulation of cell
growth and division. In the other side the study of cell signaling
crucially important in understanding how a cell can perform its
function and can lose growth control.
Cell signaling can affect virtually every aspect of cell
structure and function. An understanding of the cell signaling
requires knowledge about other types of cellular activity. Cell
signaling is also intimately involved in the regulation of cell
growth and division. In the other side the study of cell signaling
crucially important in understanding how a cell can perform its
function and can lose growth control.
9. References
Cell and Molecular Biology, Concepts and Experiments
Gerald Karp
Gene VIII
Benjamin Lewin
Principles of Biochemistry
Lehninger
Website : www.bio.miami.edu.
Cell and Molecular Biology, Concepts and Experiments
Gerald Karp
Gene VIII
Benjamin Lewin
Principles of Biochemistry
Lehninger
Website : www.bio.miami.edu.
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