Signal Transduction in Plants

by

Dr. M. Shahbaz
Botany
 Bot-709 Signal Transduction in Plants 3(3-
0)
Signaling; Receptors involved in signaling: their nature and location on the cellular
membranes; Mitogens; Secondary messengers in plants: Types, nature, role and mechanisms
of action; Cascades of reactions and gene expression; Hormones as signaling agents;
Environmental induction of signaling; Factors affecting signaling in plants; Mutants:
Mutagens and types of mutation; Use of mutants in understanding signaling phenomena in
plants; Gene regulation and signal transduction in prokaryotes and eukaryotes; Signal
transduction in space and time.
Suggested Readings:
 
1.Gomperts, B.D., J.M. Kramer and P.E.R. Tatham. 2009. Signal Transduction. 2 nd Ed.
Elsevier, San Diego, CA, USA.
2.Jones, R., H. Ougham, H. Thomas and S. Waaland. 2013. The Molecular Life of Plants.
American Society of Plant Biologists and Wiley-Blackwell, Oxford, UK.
3.Pfannschmidt, T. 2008. Plant Signal Transduction: Methods and Protocols (Methods in
Molecular Biology). Humana Press, Laurel, MD, USA.
4.Taiz, L., E. Zeiger, I.M. Møller and A. Murphy. 2015. Plant Physiology and Development,
6th Ed. Sinauer Associates Inc., Sunderland, MA, USA.
5.Yoshioka, K. and K. Shinozaki. 2009. Signal Crosstalk in Plant Stress Responses. Wiley-
Blackwell, Oxford, UK.
Components of signal transduction
Environmental or
Physiological signal

Receptor

Signal transduction pathway

Response
 Environmental: light, temp., touch etc.
Physiological: Hormone, nutrient etc.

Receptor kinase, G protein-coupled receptor

Kinase, calcium, lipids, pH

Gene expression, cytoskeleton, enzyme

activity
 Signal transduction
• Charles Darwin (1881) – Phototropic
growth responses in canary grass and oat
seedling
• Unidirectional light source at the
coleoptile's tip but bending response took
place further back along the shoot. Later
on this signal was discovered as auxin
• Receptors: Specialized sensor proteins
perceive external or internal signals

• Transduce signal (convert it from one

form to other) to amplify signal and trigger
cellular response

• Some time receptors do this job by

modifying the activity of other proteins
and/or employing intracellular signaling
molecules – secondary messengers
 Signal transduction
• One of the milestone of plant signal
transduction research in mid-twentieth
century is the identification of the
photoreceptors – phytochrome
• In late 1980s advent of molecular genetic
studies in model plant Arabidopsis thaliana
led to an explosion of knowledge about
signal transduction in plants
• Every class of hormone has specific
receptors which have been identified
through genetic approaches
Plant Responses to Internal and
External Signals
• Linnaeus noted that flowers of different species
opened at different times of day and could be
used as a horologium florae, or floral clock
• Plants, being rooted to the ground, must
respond to environmental changes that come
their way
• For example, the bending of a seedling toward
light begins with sensing the direction, quantity,
and color of the light
 Signal transduction pathways link
signal reception to response
• Plants have cellular receptors that detect
changes in their environment
• For a stimulus to elicit a response, certain
cells must have an appropriate receptor
• Stimulation of the receptor initiates a
specific signal transduction pathway
 Examples
• A potato left growing in darkness produces
shoots that look unhealthy and lacks
elongated roots
• These are morphological adaptations for
growing in darkness, collectively called
etiolation
• After exposure to light, a potato undergoes
changes called de-etiolation, in which
shoots and roots grow normally
(a) Before exposure to light (b) After a week’s exposure to
natural daylight
• A potato’s response to light is an example
of cell-signal processing
• The stages are reception, transduction,
and response
 CELL CYTOPLASM
WALL

1 Reception 2 Transduction 3 Response

Relay proteins and Activation

of cellular
second messengers responses

Receptor

Hormone or
environmental
stimulus Plasma membrane
• Reception
• Internal and external signals are detected
by receptors, proteins that change in
response to specific stimuli
• Transduction
• Second messengers transfer and amplify
signals from receptors to proteins that
cause responses
 1 Reception 2 Transduction

CYTOPLASM
NUCLEUS
Specific
Plasma cGMP
protein
membrane kinase 1
Second messenger activated
produced
Phytochrome
activated
by light
Cell
wall

Light
 1 Reception 2 Transduction

CYTOPLASM
NUCLEUS
Specific
Plasma cGMP
protein
membrane kinase 1
Second messenger activated
produced
Phytochrome
activated
by light
Cell
wall Specific
protein
kinase 2
activated

Light

Ca2+ channel
opened

Ca2+
 1 Reception 2 Transduction 3 Response
Transcription
CYTOPLASM factor 1
NUCLEUS
Specific
Plasma cGMP
protein P
membrane kinase 1
Second messenger activated
produced Transcription
Phytochrome factor 2
activated
by light P
Cell
wall Specific
protein
kinase 2
activated
Transcription

Light

Translation

De-etiolation
Ca2+ channel (greening)
opened response
proteins

Ca2+
 Response
• A signal transduction pathway leads to
regulation of one or more cellular
activities
• In most cases, these responses to
stimulation involve increased activity of
enzymes
• This can occur by transcriptional
regulation or post-translational
modification
 Transcriptional Regulation
• Specific transcription factors bind directly
to specific regions of DNA and control
transcription of genes
• Positive transcription factors are proteins
that increase the transcription of specific
genes, while negative transcription factors
are proteins that decrease the
transcription of specific genes
 Post-Translational Modification of
Proteins
• Post-translational modification involves
modification of existing proteins in the
signal response
• Modification often involves the
phosphorylation of specific amino acids
De-Etiolation (“Greening”) Proteins
• Many enzymes that function in certain
signal responses are directly involved in
photosynthesis
• Other enzymes are involved in supplying
chemical precursors for chlorophyll
production
Signal Transduction in
Prokaryotes and
Eukaryotes
 Signal Transduction
• Cells respond to their environment by re-organizing their
structure, regulating the activity of proteins and altering
patterns of gene expression. The stimulus for such
responses is known as signal. It may be a small molecule, a
macromolecule or a physical agent such as light,
temperature, water etc. Signals interact with the responding
cell through specific molecules called receptors.
• Small molecules often act as diffusible signals. In unicellular
organizations diffusible signals may be environmental or
may be released from other cells e.g. yeast mating-type
pheromones or cAMP in Dictyostelium. In metazoans,
signals may be released from nearby cells and diffuse over
short distances (Paracrine signaling), or they may be
released from distant cells and reach their target through
vascular system (endocrine signaling). Macromolecular
signals are associated with the extracellular matrix or
displayed on the surface of neighboring cells (Juxtacrine
signaling). A molecular signal that binds to a receptor is
called ligand.
 Signal Transduction in Prokaryotes
• Animal (mammals) possess a well developed nervous system
by which they are able to sense and respond to environment.
• Many processes such as (1) stimulus detection (2) signal
amplification (3) appropriate output responses are present in
all cell sensory systems including bacteria.
• Many bacterial signaling pathways consist of molecular units
called transmitters and receivers. This is called two-
component regulatory system.
• Bacteria use two component regulatory systems to sense
extracellular signals. They sense chemicals in the environment
by means of a small family cell surface receptors, each
involved in the response to a specific group of chemicals
called ligands. A protein in the plasma membrane of bacteria
binds directly to a ligand or binds to a soluble protein that has
already attached to the ligand, in the periplasmic space
between the PM and the cell wall.
• Upon binding, the membrane protein undergoes a
conformationational change that passes across the membrane
to the cytosolic domain of the receptor protein. This
conformational change initiates the signaling pathway that
leads to the response.
 Signaling via bacterial two-component-systems

• The sensor protein present on cell wall detects

the stimulus via the input domain and transfers
the signal to the transmitter domain by means of
conformational change (first dashed arrows).
The transmitter domain of the sensor then
communicates with the response regulator by
protein phosphorylation of the receiver domain.
Phosphorylation of the receiver domain induces
a conformational change (second dashed
arrows) that activates the output domain and
brings about the cellular response.
• For instance, osmoregulation, chemotaxis and
sporulation are regulated by two component
systems.
• The signal is passed from transmitter domain to
receiver domain due to protein phosphorylation.
Transmitter domains have the ability to
phosphorylate themselves using ATP on a histidine
near the amino terminus. Because of this
autophosphorylation, the sensor proteins containing
transmitter domains are called autophosphorylating
histidine kinases. Immediately after the transmitter
domain becomes autophosphorylated on a histidine
residue the (P) is transferred to a specific aspartate
residue near the middle of the receiver domain of the
response regulator protein. As a result, the aspartate
residue becomes phosphorylated. Phosphorylation of
the aspartate residue causes the response regulator
to undergo a conformational change that results in
activation.
Parkinson (1993)
 Signal Transduction in Eukaryotes
• There are many eukaryotic microorganisms which use
chemical signals in cell to cell communication. e.g.

– (1) in Dictyostelium (a slime mold) starvation induces certain cells

to secrete cyclic AMP (cAMP). The secreted cAMP diffuses out
and causes the nearby cells to aggregate into a colony.
– (2). A similar example is that of yeast mating which occurs due to
chemical communication.

• In complex multi-cellular organisms two main systems

have been evolved
– (i) nervous system
– (ii) endocrine system
• In contrast, plants lack nervous system but they have
evolved hormones as chemical messengers. However,
generally plant signal transduction pathways differ to a
great extent from those of animals. But nevertheless there
are some common signal mechanisms in both animals
and plants that we are discussing here.
 Hormones

• There are two classes of hormones depending

on their ability to move across the plasma
membrane.
– Lipophilic hormones: which diffuse readily across the
hydrophobic bilayer of plasma membrane e.g.
Androgens, glucocorticoids, estrogens and
brassinosteroids.
– Water soluble hormones which are unable to enter
the cell by their own e.g. antidiuretic hormone (ADH),
glucagons, Thyroid Stimulating Hormone (TSH)
• Lipophilic hormones bind mainly to receptors in the
cytoplasm or nucleus, whereas water soluble
hormones bind to receptors located on the cell
surface.
• In both cases ligand binding changes the receptor by
causing a conformational change.
• Some receptors such as steroid hormone receptors
can regulate gene expression directly.
• But in most cases the receptor initiates one or most
sequences of biochemical reactions that connect the
stimulus to a cellular response. Such a sequence of
reactions is called a signal transduction pathway.
• The final or end result of signal transduction
pathways is to regulate transcription factors which in
turn regulate gene expression.
 Signal transduction pathways
• Signal transduction pathways often involves generation
of second messengers. They actually transmit secondary
signals inside the cell that greatly amplify the original
signal. e.g. a single hormone molecule might lead to the
activation of an enzyme that produces hundreds of
molecules of a second messenger. Most common
second messengers are cAMP, cGMP, 1,2 diacylglycerol
(DAG), or inositol 1,4,5 triphosphate or inositol 4,5,6
triphosphate (IP3) and Ca2+. Hormones binding normally
causes enhanced levels of one or more of these second
messengers resulting in the activation or inactivation of
enzymes or regulatory proteins. Protein kinases and
phosphatases are usually involved in most of the cases.
 Steroid Receptors can act as transcription factors
• Steroid Receptors can act as transcription factors. Almost all
the steroid hormones can freely pass through the PM because
of their lipophilic/hydrophobic nature and they bind to the intra-
cellular receptors proteins. On binding, these proteins function
as transcription factors. All such steroid receptor proteins have
similar DNA binding domains. Steroid response elements are
typically located in enhancer regions of steroid stimulated
genes.
• Most steroid receptors are localized in the nuclear, where they
get anchored to nuclear proteins in an inactive form. When the
receptor binds to the steroid, it is released from the inactive
anchor protein and becomes activated as a transcription factor.
The activated transcription factor then binds to the enhancer
and stimulates transcription.
• Not all intracellular steroid receptors are localized in the
nucleus. The receptor for cortisol (glucocorticoid hormone)
differs from the others in that it is located in the cytosol,
anchored in an inactive cytosolic protein. Binding of the
hormones causes the release of the its cytosolic inhibitor and
the receptor-hormone-complex then migrates into the nucleus
where it binds to the enhancer and stimulates transcription.
• Although most studies on animal steroid hormones
have focused on their role in regulating gene
expression via receptors that act as transcription
factors, recently brassinosteroid has been found as a
steroid hormone in plants. The receptor for this
hormone has also been discovered which is a trans-
membrane leucine rich repeat receptor.
• Every receptor has two functional domains i) a
recognition domain binds the hormone ---- binding
ii) the second region generates a signal that couples
hormone recognition to some intracellular function
---coupling
 Transport of water soluble hormones into the cell
• The cell surface receptors of water soluble hormones can interact
with G-proteins (GPCRs) G-protein-coupled receptors
• All water soluble (hydrophilic) hormones of mammals bind to cell
surface receptors. The cell receptors interact with signal –
transducting GTP binding proteins known as heterotrimeric G
proteins. The activated G proteins, in turn, activate an effector
enzyme. The activated effector enzyme generates an intracellular
second messenger, which stimulates numerous cellular
processes.
• Receptors using G-proteins are structurally similar but functionally
different. The receptor proteins consist of seven trans-membrane
 helices which are known as seven arch spanning, seven-pas
or serpentine receptors.
• Heterotrimeric G proteins cycle b/w active and inactive forms
The G proteins that transmit/transduce the signals from the seven-
spanning receptors are called heterotrimeric G-Proteins because
they consist of three different submits, ,  and . The
heterotrimeric G-proteins act as molecular switches b/w active and
inactive forms. The  &  subunits form a tight complex that
anchors the trimeric G protein to the membrane on the
cytoplasmic side.
Schematic diagram of the general structure of G protein-coupled receptors
All receptors of this type have the same orientation in the membrane
Contain seven transmembrane α-helical regions (H1-H7)
Four extracellular segments (E1-E4)
Four cytosolic segments (C1-C4)
The carboxylic-terminal segment (C4), the C3 loop, and , in some receptors, also the
C2 loop are involved in interactions with a coupled trimeric G protein
• The G-protein becomes activated after binding
to the activated seven-spanning receptor. In an
inactive form, G exists as a trimer with GDP
bound to the . Binding to the receptor – ligand
complex induces the  to exchange GDP for
GTP. The exchange causes the  – submit to
associate with an effector enzyme.
• The  submit has a GTPase activity that is
activated when it binds to the effector enzyme
e.g. adenylyl cyclase. GTP is hydrolyzed to GDP
thereby inactivating the  subunit, which in turn
inactivates adenylyl cyclase. The  subunit
bound to GDP re-associates with the  and 
subunits, and it starts another cycle to bind to
the hormone-receptor complex.
 Activation of adenylyl cyclase increases the level
of cyclic AMP
• cAMP is an important signaling molecule in
prokaryotes, animal cells, and plant cells. In
higher animals, adenylate cyclase is an integral
membrane protein that contains two
clusters/groups of six-membrane spanning
domains, two of which extending into the
cytoplasm as catalytic domains. Activation of
adenylyl cyclase by heterotrimeric G proteins
increases the conc. of cAMP in the cell, which is
normally maintained at a low level by the action
of cAMP phosphodiesterase which hydrolyzes
cAMP to 5 AMP.
 cAMP Functions in Animals

• 1. About all the effects of cAMP in animal cells are brought about by
the enzyme protein kinase A (PKA). In un-stimulated cells, PKA is in
the inactive form b/c of the presence of a pair of inhibitory subunits.
cAMP binds to the inhibitory subunits, causing them to dissociate
from the two catalytic subunits, thereby activating the catalytic
subunits. The activated catalytic subunits then are able to
phosphorylate specific serine or threonine subunits of selected
proteins which may also be protein kinases e.g. activation of
glycogen phosphorylase by PKA in animal muscles.
• 2. In cells in which cAMP regulates gene expression, PKA
phosphorylates a transcription factor called CREB (Cyclic AMP
response element – binding protein). Upon activation by PKA,
CREB binds to the cAMP response element (CRE) which is located
in the promoter regions of genes that are regulated by cAMP.
• 3. cAMP also interacts with specific cAMP – gated cation channels.
It binds to and opens Na+ channels on the PM, resulting in Na+
influx and membrane depolarization.
 Function of cAMP in plants

• Because of low levels of cAMP detected in plants, the

role of cAMP in plant signal transduction has been highly
controversial (Assmann, 1995). But there is an
accumulating evidence confirming the role of cAMP in
plants. e.g. pollen tube growth in lilly has been shown to
be stimulated by conc. of cAMP as low as 10 nM.
• cAMP has also been found activating K+ channels in the
PM of faba beans mesophyll cells (Li et al. 1994).
• Ichikawa et al. (1997) identified genes for adenylyl
cyclase in tobacco and Arabidopsis.
 IP3- second messenger of water soluble hormones
Activation of Phospholipase C initiates the IP3 pathway

Calcium serves as a second messenger for many signaling events

in both animals and plants. The concentration of free Ca2+ in the
cytosol is very low (0.1 µM). Ca-ATPases on PM and ER pump
calcium out of cell and into the ER lumen, respectively. In plant cells
most of the Ca of the cell accumulates in the vacuole. The transport
of Ca at tonoplast is carried out by proton pumps via Ca2+-H+
antiporter.
• In animal cells, certain hormones can induce a transient rise in the
cytosolic Ca up to 5 µM. The rise in cytosolic Ca occurs due to
opening of intracellular compartments. The coupling of hormone
binding to the opening of intra-cellular Ca channels is mediated by
another second messenger IP3.
• Phosphatidylinositol (PI) is a minor phospholipid component
of cell membrane which can be converted to PI phosphate
(PIP) and PI bisphosphate (PIP2) by kinases. PIP2 though not
abundant as PI, it plays a crucial role in signal transduction.
The activated phospholipase C (PLC) readily hydrolyzes PIP2
to give rise IP3 and diacylglycerol (DAG). They both play
important role in cell signaling.
• The IP3 generated by activated phospholipase – C diffuses
through the cytosol and binds to IP3 binding sites on the ER
and tonoplast. These binding sites are IP3 – gated Ca2+
channels that open when they bind to IP3. Ca diffuses into
cytosol and causes a cellular response. This response is
terminated when IP3 is broken down by specific
phosphatases or when the released Ca is pumped out of the
cytoplasm by Ca2+ - ATPases.
• The Ca signal often originates in a localized region of the cell
and propagates as a wave throughout the cytosol. Repeated
waves called Ca oscillations can follow the original signal,
each lasting from a few sec to several minutes. The oscillation
may play a role in avoiding the toxicity that results form high
conc. of Ca in the cytosol.
 PI/PLC signalling

signal

out receptor

Plasma membrane
G
PLC
PI PIP PIP2 DAG

in
InsP3 PKC
Ca2+ +
Ca 2+

Ca2+
Ca2+ Ca2+

Protein kinase calmodulin enzymes

Intracellular responses
phosphatidylinositol (PI)
 Animal (13):
PLC
PLC Plant (9) / yeast (1)
Plant PI/PLC PLC
signalling signal
PLC
PLC
PLC
out receptor PLC

x PLC
Plasma membrane
G PLD
PI PIP PIP2 DAG PA DGPP

in

+
x
InsP3
InsP6 x
PKC PK

x
Ca 2+

Ca 2+

Ca2+
Membrane trafficking
regulation of Ion channels Ca2+ Ca2+
& Cytoskeleton

Protein kinase calmodulin enzymes

Intracellular responses
Plant PI/PLC signaling: Differences and similarities to the mammalian paradigm.
Higher plants lack both InsP3 receptor, a ligand-gated Ca2+ channel, and protein
kinase C (PKC); hence, these are striked-out (X). Instead, plants seem to use their
phosphorylated products, InsP6 and phosphatidic acid (PA), as signaling
molecules. PA can also be generated by PLD and is attenuated by PA kinase
(PAK), a novel lipid kinase that is absent from mammalian cells. PAK generates
diacylglycerolpyrophosphate (DGPP), which might function as a signaling
molecule itself. Plant PLCs belong to the PLCz subfamily. It is not known how
they are regulated but not through heterotrimeric G-proteins (G), which is
therefore striked out. Plant PtdIns(4,5) P2 (PIP2) quantities are extremely low, and
plant PLCs lack the PH domain. Instead, PtdIns4P (PIP) is a better candidate to be
the in vivo PLC substrate. The resulting InsP2 can be phosphoryated to InsP6 via
two dual-specificity inositolpolyphosphate kinases (IPK), while DG is
phosphorylated to PA via DGK. Evidence is also emerging that PtdIns4P and
PtdIns(4,5)P2 themselves function as signaling molecules, involving membrane
trafficking, organization of the cytoskeleton, and regulation of ion channels. In
such a scenario, PLC would function as an attenuator of PIP and PIP2 signaling.
Solid arrows indicate metabolic conversions. Dashed arrows represent mechanisms
of regulation.
 Diacylglycerol activates protein kinase C

• Breakdown of PIP2 by phospholipase C produces IP3 and

DAG. IP3 being hydrophilic diffuses rapidly into the
cytoplasm but DAG being a lipid remains in the
membrane. In animal cells DAG can come close to
protein kinase C (PKC) and activates it. The PKC is
located in the cytosol in an inactive form, but upon
binding to the Ca2+ it undergoes conformational change
and associates with a PKC receptor protein that
transports it to the inner surface of the PM where it
encounters DAG. PKC activity has also been detected in
plants. G proteins, phospholipase C and various protein
kinases have been discovered in plant membranes.
However, there is little evidence available that activation
of PKC by DAG has some role in signaling.
 Role of Ca - Calmodulin (Ca-modulated protein (CaM)) in
activation of Protein kinases -- act as on-off switches
• In addition to directly binding of Ca2+ with some proteins, such
as channels, most of the effects of Ca2+ are due to its binding to
regulatory proteins such as Calmodulin (17 kDa 148 amino
acids). Calmodulin widely occurs in eukaryotes both animals
and plants but it is absent in prokaryotes.
• There are some other Ca-binding proteins in addition to
calmodulin that possess a similar Ca-binding site e.g. in protein
parvalbumin (EF hand = E & F are two ά helices)
• Each calmodulin molecule binds 4 Ca2+ ions and changes
conformation thereby enabling it to bind and activate other
proteins. Ca2+ - calmodulin can stimulate some enzymes
directly such as PM Ca2+ -ATPase which pumps Ca2+ out of the
cell. In addition, most of the effects of Ca2+ are brought about by
activation of Ca2+ - calmodulin dependent protein kinases (CaM
kinases). The CaM kinases phosphorylate serine or threonine
residues of their target enzymes, causing enzyme activation.
 Enzymes regulated by Ca or Calmodulin

• Adenylyl cyclase
• Ca – dependent protein kinase
• Ca2+ Mg2+ - ATPase
• NAD Kinase
• Phospholipase kinase
• PA carboxylase
• PA dehydrogenase
• PA kinase
• The most common protein kinases in
plants are Ca-dependent protein kinases
(CDPKs). CDPKs are activated by Ca2+
but are insensitive to calmodulin. CDPKs
have been recently found to regulate anion
channels on the tonoplast and are also
involved as a component of the ABA
signaling pathway.
 Some water soluble hormones bind to Receptor
Tyrosine Kinases (RTK)
• About 50 RTKs have been characterized. They are divided into 14
families based on structure.
• In animals cells, RTKs are the important class of cell surface
receptors although they have not yet been reported in plants. The
RTK possess a hormone ligand-binding domain, a trans-
membrane domain, and catalytic domain (in cytosol). Since the
trans-membrane domain consists of a single ά helix, the hormone
cannot transmit a signal directly to the cytosolic side. However,
binding of the hormone to the receptor induces dimerization of
adjacent receptors which allows the two catalytic domains to come
into contract and autophosphorylate the tyrosine residues.
• On auto-phosphorylation, the catalytic site of the RTKs binds to
different cytosolic signaling proteins. After binding to the RTK, the
inactive signaling protein is itself phosphorylated on specific
tyrosine residues. Some transcription factors are activated like this.
However, the signaling initiated by RTKs begins with the small
monomeric (only ά unit) G proteins called as Ras.
• There are three common monomeric G proteins: Ras,
Rab and Rho/Rac. All belong to Ras super-family of
monomeric GTPases. Rho and Rac relay signals from
surface receptor to the actin cytoskeleton, whereas
members of the Rab family of GTPases are involved in
regulating intracellular membrane vesicle traffic. Ras
proteins transmit signals from RTKs to the nucleus.
Ras is a G protein that cycles b/w an inactive GDP –
binding form and an active GTP – binding form. Ras
can also act as GTPase to hydrolyze bound GTP to
GDP thereby terminating the response. Ras has not
yet been discovered in plants.
• Binding of hormone to the RTK induces dimerization followed by
auto-phosphorylation of the catalytic domain. Auto-
phosphorylation of the receptor causes binding to the Grb2
protein which is tightly bound to another protein known as Sos.
The Grb –Sos complex then attaches to the RTK. Upon binding
to Sos, Ras exchanges GDP with GTP and Ras then becomes
active.
• The activated Ras is then able to bind to another soluble
serine/threonine kinase known as Raf. Upon binding to Ras, Raf
becomes active and initiates a chain of phosphorylation
reactions called the MAPK cascade. In plants the ethylene
receptors pass signals to a protein kinase of Raf family.
• MAPK (mitogen – activated protein kinase) cascade refers to a
series of protein kinases that phosphorylate each other in a
specific sequence. Ultimately, the phosphorylated MAPK enters
the nucleus and activates transcription factors. The activated
transcription factors then stimulate gene expression.
Ras Signaling Pathway
 Different steps of ligand-induced activation of receptor tyrosine
kinase (RTKs) and cytokine receptors
Step 1
In both types of receptors, ligand binding causes a conformational change that
promotes formation of a functional dimeric receptor, bringing together two
intrinsic or associated kinases, which then phosphorylate each other on a
tyrosine residues in the activation lip.
Step 2
Phosphorylation causes the lip to move out of the kinase catalytic site, thus
allowing ATP or a protein substrate to bind. The activated kinase then
phosphorylates other tyrosine residues in the receptor’s cytosolic domain.
Step 3
The resulting phosphotyrosines function as docking sites for various signal-
transduction proteins.
General structure and ligand-induced activation of receptor
tyrosine kinase (RTKs) and cytokine receptors
General structure and ligand-induced activation of receptor
tyrosine kinase (RTKs) and cytokine receptors