BY:

KUMAR KASHYAP

M. TECH MARINE BIOTECHNOLOGY

(NCAAH)

CUSAT

Signal transduction

Signal + Transductions

Any function that conveys some information

To forward

Cells have the ability to respond to the signals

generated far from the plasma membrane.

The bacterial cells have membrane proteins present on

the surface of plasma membrane. The membrane

proteins analyse the surrounding environment for pH

change, osmotic strength, the availability of food,

oxygen, and light, and the presence of harmful

chemicals, predators and competitors for food. A signal

is generated for conveying the above information. The

bacterial cell then response to the information by like,

moving towards the food, away from the predators

harmful chemicals or forming spore in nutrient

depleting environment.

Bacteria

pH change

Osmotic

change

Availability of

food, oxygen and

light

Presence of

harmful chemicals,

predators or

competitors for

food

Talking about the multi cellular organisms,cells performing different functions exchangea variety of signals.

For example, plant cells respond to growthhormone and sunlight.

In animals this communication takes place ina broader way. Cells exchange informationabout the change in concentration of ionsand glucose in the extra cellular fluids, inembryo the correct placement of cells duringdevelopment, etc.

Signal transduction is a very specific and very sensitive bio-chemical

process. A particular type of signal is received by a particular type of

receptor only. The interaction’s specificity is almost similar to that of

substrate-enzyme interaction or antigen-antibody interaction.

In multicellular organisms, the specificity is a little bit more complex. This

is because in multicellular organisms, a particular type of signal is received

by a particular type of receptor only and these receptors are present on

specific cells only.

The sensitivity of the signal transduction sometimes gets modified. When a

signal is present for a longer time, desensitization of the receptor occurs;

when the signal falls below a certain threshold the receptor becomes

sensitive again.

One of the most important features of the signal transduction is

Integration. It is the ability of the system to receive multiple signals and

produce a single response. How does this occurs? This occurs because

different pathways converge at different levels.

The trigger for each signal transduction system is different but the general

features are common to all. A signal interacts with a receptor; the activated

receptor interacts with the cellular machinery, producing a second signal or

changing the activity of cellular protein; the metabolic activity of the cell

under goes a change and finally the transduction ends.

Now let’s have a look on type of receptors:

G protein coupled receptors. They indirectly activate enzymes thatgenerate intra-cellular secondary messengers.

Receptor tyrosine kinase. They are plasma membrane receptors thatalso act as enzymes. When these are activated by their extracellularligands, they catalyze the phosphorylation of several cytosolic orplasma membranes proteins.

Receptor guanylyl cyclases. They are also plasma membranereceptors with an enzymatic cytoplasmic domain. The intracellularsecond messenger for these receptors, cGMP, activates a cytosolicprotein kinase that phosphorylates cellular proteins and therebychanges their activities.

Gated ion channels of the plasma membrane that open and close inresponse to the binding of chemical ligands or changes intransmembrane potential.

Adhesion receptors that react with the macromolecular component ofthe extracellular matrix and convey instructions to the cytoskeletolsystem about cell migration or adherence to the matrix.

Nuclear receptors that bind specific ligands and alter the rate at whichspecific genes are transcribed and translated into cellular proteins.

IMPORTANT PATHWAYS OF SIGNAL TRANSDUCTION

G-Protein Coupled Receptors and Second Messengers•There are three important components of signal transduction through G

protein-coupled receptors – a plasma membrane receptor with seven

transmembrane helical segments, an effector enzyme in the plasma

membrane that generates an intracellular second messenger, and a guanosine

nucleotide-binding protein that activates the effector enzymes.

It is a large family of plasma membrane receptors with intrinsic protein

kinase activity.

Receptor tyrosine kinase have a ligand binding domain on the extra cellular

face of the plasma membrane and an enzyme active site on the cytoplasmic

phase.

Insulin regulates both metabolic enzymes and gene expression. Insulin

does not enter cells, but initiates a signal that travels a branched pathway

from the plasma membrane receptor to insulin-sensitive enzymes in the

cytosol and to the nucleus, where it stimulates the transcription of specific

genes.

The active insulin receptor protein (INS-R) consists of two identical

subunits protruding from the outer face of the plasma membrane and two

transmembrane subunits with their carboxyl termini protruding into the

cytosol.

Jak Stat pathway is the system that regulates the formation of erythrocytes

in mammals.

The signal for this system is erythropoietin, a 165 amino acid protein

produced in the kidneys.

Guanylyl cyclases are receptors enzymes, that when activated,

convert GTP to cGMP.

In animals, the action of these cGMP are mediated by cGMP-

dependent protein kinases also called as protein kinase G

(PKG).

The cGMP so produced is a second messenger that activates

cGMP-dependent protein kinase (PKG). This enzyme alters

metabolism by phosphorylating Ser and Thr residues in targets

proteins.

Bacteria responds to nutrients in its environment, including sugars and

amino acids, by swimming towards them, propelled by one or a fewflagella.

When an attractant ligand (A) binds to the receptor domain of the

membrane-bound receptor, a protein His kinase in the cytosolic domain

(component 1) is activated and autophosphorylates a His residue.

This phosphoryl group is then transferred to an Asp residue on component

2 (in some cases, as shown here, a separate protein; in others, another

domain of the receptor protein).

After phosphorylation, component 2 moves to the base of the flagellum,

where it reverses the direction of rotation of the flagellar motor.

Two-component systems have been detected in many other bacteria, both

gram-positive and gram-negative, and in archaea, as well as in protists and

fungi.

Like animals, vascular plants must have a means of communication

between tissues to coordinate and direct growth and development; to adapt

to conditions of O2, nutrients, light, temperature, and water availability;

and to warn of the presence of noxious chemicals and damaging pathogens.

Plants Detect Ethylene through a Two-Component System and a MAPK

Cascade. The gaseous plant hormone ethylene (CH2CH2), which stimulates

the ripening of fruits (among other functions), acts through receptors that

are related in primary sequence to the receptor His kinases of the bacterial

two-component systems and probably evolved from them.

The ethylene receptor (pink) in the endoplasmic reticulum is a two-

component system contained in a single protein, with a receptor domain

(component 1) and a response regulator domain (component 2). The

receptor controls (in ways we do not yet understand) the activity of CTR1,

a protein kinase similar to MAPKKKs and therefore presumed to be part of

a MAPK cascade.

David L. Nelson, Michael M. Cox, “Lehninger – Principles of

Biochemistry”, - Fifth edition.

J. Koolman, K. H. Roehm, “Color Atlas of Biochemistry”, - Secon editon.