Signal Transduction Pathways

“ From signal to gene expression”

Signal Transduction Pathways

The biochemical events that conduct the signal of a hormone or growth factor

from the cell exterior, through the cell membrane and into the cytoplasm which involve a number of molecules including

receptors, proteins, and messengers

a series of steps by which a signal on a cell’s surface is converted into a specific

cellular response

1. The stream of signals to which plant cells react is continuous and complex

2. Signal transduction uses a network of interactions within cells, and throughout the plants

Overview on Plant Signal Transduction

Analogy view of cell signaling transduction pathway

Input (command)Keyboard

Signalperception

Endogenous:phytohormoneExogenous:environmental cue

CPU (Central

Processing Unit)ChipSignal

Transduction NetworkCompiling, Integration,processing

Output (performance

)PrinterSignal

ResponseMorphogenesis change,Growth development differentiation

EXTRACELLULARFLUID

Reception

Plasma membrane

Transduction CYTOPLASM

Receptor

Signalmolecule

EXTRACELLULARFLUID

Reception

Plasma membrane

Transduction CYTOPLASM

Receptor

Signalmolecule

Relay molecules in a signal transductionpathway

EXTRACELLULARFLUID

Reception

Plasma membraneTransduction CYTOPLASM

Receptor

Signalmolecule

Relay molecules in a signal transductionpathway

Response

Activationof cellularresponse

1. The stream of signals to which plant cells react is continuous and complex

2. Signal transduction uses a network of interactions within cells, and throughout the plants

Overview on Plant Signal Transduction

STIMULUS

R

R

Ca2+

Ca2+

G-prot

Kin

Phos

TF

Plasmamembrane

Nuclear membrane

DNA

Signal transduction (Simplified model)

Stimulus Hormones, physical environment, pathogensReceptor On the plasmamembrane, or internalSecondary messengers Ca2+, G-proteins, Inositol PhosphateEffector molecules Protein kinases or phosphatases Transcription factorsResponse Stomatal closure Change in growth direction

Signal Transduction Components

How many signal factors whichPlant will respond to? --biotic and abiotic factors--

STIMULUS

Stimulus

Reception

The binding between a signal molecule (ligand) and receptor is highly specific

– A conformational change in a receptor is often the initial transduction of the signal

– Most signal receptors are plasma membrane proteins

A signal molecule binds to a receptor protein, causing it to change shape

Intracellular Receptors

• Some intracellular receptor proteins are found in the cytosol or nucleus of target cells

• Small or hydrophobic chemical messengers can readily cross the membrane and activate receptors

• An activated hormone-receptor complex can act as a transcription factor, turning on specific genes

Receptors in the Plasma Membrane

• Most water-soluble signal molecules bind to specific sites on receptor proteins in the plasma membrane

• There are three main types of membrane receptors:1. G-protein-linked receptors2. Receptor tyrosine kinases3. Ion channel receptors

• It is a plasma membrane receptor that works with the help of a G protein

• The G-protein acts as an on/off switch• If GDP is bound to the G protein, the G protein

is inactive

G-protein-linked Receptor

Segment thatinteracts withG proteins

Signal-binding site

G-protein-linked receptor

• Regulates cell growth and cell reproduction

• Tyrosine kinase catalyzes transfer of phosphate group from ATP to tyrosines

• Can trigger ten or more signal transduction pathways at once

• Abnormal tyrosine kinases that work even without a signal molecule may contribute to some cancers

Receptor Tyrosine Kinases

Signalmolecule

Helix in themembrane

Signal-binding site

Tyr

Tyr

Tyr Tyr

Tyr

TyrTyrosines

Receptor tyrosinekinase proteins(inactive monomers)CYTOPLASM

Tyr

Tyr

Tyr Tyr

Tyr

Tyr Tyr

Tyr

Tyr Tyr

Tyr

Tyr

Tyr

Tyr

Tyr Tyr

Tyr

Tyr

Activated tyrosine-kinase regions(unphosphorylateddimer)

Signalmolecule

Dimer

Fully activated receptor tyrosine-kinase(phosphorylateddimer)

Tyr

Tyr

Tyr Tyr

Tyr

TyrPPP

PPPATP 6 ADP

Tyr

Tyr

Tyr Tyr

Tyr

TyrP

PP

PPP

Inactiverelay proteins

Cellularresponse 2

Cellularresponse 1

Activated relay proteins

6

• Acts as a gate when the receptor changes shape

• Signal molecule binds as a ligand to the receptor, the gate allows specific ions, such as Na+ or Ca2+, through a channel in the receptor

Ion Channel Receptor

Receptor

Receptor

Receptor

Receptor

Receptor

Receptor

Transduction

• Transduction usually involves multiple steps

• Multistep pathways can amplify a signal: A few molecules can produce a large cellular response

• Multistep pathways provide more opportunities for coordination and regulation

Cascades of molecular interactions relay signals from receptors to target molecules in

the cell

Signal Transduction Pathways

The molecules that relay a signal from receptor to response are mostly proteins

Like falling dominoes, the receptor activates another protein, which activates another, and so on, until the protein producing the response is activated

At each step, the signal is transduced into a different form, usually a conformational change

Protein Phosphorylation and Dephosphorylation

In many pathways, the signal is transmitted by a cascade of protein phosphorylations Phosphatase enzymes remove the

phosphates This phosphorylation and

dephosphorylation system acts as a molecular switch, turning activities on and

off

Signal molecule

Activated relaymolecule

Receptor

Inactiveprotein kinase

1 Activeprotein kinase

1

Inactiveprotein kinase

2 Activeprotein kinase

2

Inactiveprotein kinase

3 Activeprotein kinase

3

ADP

Inactiveprotein

Activeprotein

Cellularresponse

Phosphorylation cascade

ATP

PPP i

ADPATP

PPP i

ADPATP

PPP i

P

P

P

Small Molecules and Ions as Second Messengers

Second messengers are small, nonprotein, water-soluble molecules or ions

The extracellular signal molecule that binds to the membrane is a pathway’s “first messenger”

Second messengers can readily spread throughout cells by diffusion

Second messengers participate in pathways initiated by G-protein-linked receptors and receptor tyrosine kinases

Cyclic AMP Cyclic AMP (cAMP) is one of the most widely used

second messengers Adenylyl cyclase, an enzyme in the plasma

membrane, converts ATP to cAMP in response to an extracellular signal

Many signal molecules trigger formation of cAMP Other components of cAMP pathways are G proteins,

G-protein-linked receptors, and protein kinases cAMP usually activates protein kinase A, which

phosphorylates various other proteins Further regulation of cell metabolism is provided by

G-protein systems that inhibit adenylyl cyclase

ATP Cyclic AMP AMP

Adenylyl cyclase

PyrophosphateP P i

Phosphodiesterase

H2O

cAMP

ATPSecondmessenger

First messenger(signal moleculesuch as epinephrine)

G-protein-linkedreceptor

G protein

Adenylylcyclase

Proteinkinase A

Cellular responses

GTP

Calcium ions and Inositol Triphosphate (IP3)

Calcium ions (Ca2+) act as a second messenger in many pathways

Calcium is an important second messenger because cells can regulate its concentration

A signal relayed by a signal transduction pathway may trigger an increase in calcium in the cytosol

Pathways leading to the release of calcium involve inositol triphosphate (IP3) and diacylglycerol (DAG) as second messengers

CYTOSOL

Ca2+Endoplasmicreticulum (ER)

IP3-gatedcalcium channel

IP3 (secondmessenger)

DAG

PIP2G-protein-linkedreceptor Phospholipase C

G protein

Signal molecule(first messenger)

EXTRACELLULARFLUID

GTP

CYTOSOL

Ca2+Endoplasmicreticulum (ER)

IP3-gatedcalcium channel

IP3 (secondmessenger)

DAG

PIP2G-protein-linkedreceptor Phospholipase C

G protein

Signal molecule(first messenger)

EXTRACELLULARFLUID

GTP

Ca2+ (secondmessenger)

CYTOSOL

Ca2+Endoplasmicreticulum (ER)

IP3-gatedcalcium channel

IP3 (secondmessenger)

DAG

PIP2G-protein-linkedreceptor Phospholipase C

G protein

Signal molecule(first messenger)

EXTRACELLULARFLUID

GTP

Ca2+ (secondmessenger)

Variousproteinsactivated

Cellularre-sponses