A presentation on signal transduction containing the important pathways

1. BY:
KUMAR KASHYAP
M. TECH MARINE
BIOTECHNOLOGY
(NCAAH)
CUSAT

2. Signal transduction
Signal + Transductions
Any function that
conveys some
information
To forward

4.  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.

5. Bacteria
pH change
Osmotic
change
Availability of
food, oxygen and
light
Presence of
harmful chemicals,
predators or
competitors for
food

6.  Talking about the multi cellular organisms,
cells performing different functions exchange
a variety of signals.
 For example, plant cells respond to growth
hormone and sunlight.
 In animals this communication takes place in
a broader way. Cells exchange information
about the change in concentration of ions
and glucose in the extra cellular fluids, in
embryo the correct placement of cells during
development, etc.

7.  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.

8.  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.

9.  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.

10. Now let’s have a look on type of receptors:
 G protein coupled receptors. They indirectly activate enzymes that
generate intra-cellular secondary messengers.
 Receptor tyrosine kinase. They are plasma membrane receptors that
also act as enzymes. When these are activated by their extracellular
ligands, they catalyze the phosphorylation of several cytosolic or
plasma membranes proteins.
 Receptor guanylyl cyclases. They are also plasma membrane
receptors with an enzymatic cytoplasmic domain. The intracellular
second messenger for these receptors, cGMP, activates a cytosolic
protein kinase that phosphorylates cellular proteins and thereby
changes their activities.
 Gated ion channels of the plasma membrane that open and close in
response to the binding of chemical ligands or changes in
transmembrane potential.
 Adhesion receptors that react with the macromolecular component of
the extracellular matrix and convey instructions to the cytoskeletol
system about cell migration or adherence to the matrix.
 Nuclear receptors that bind specific ligands and alter the rate at which
specific genes are transcribed and translated into cellular proteins.

12. 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.

13.  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.

15.  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.

17.  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.

18.  Bacteria responds to nutrients in its environment, including sugars and
amino acids, by swimming towards them, propelled by one or a few
flagella.
 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.

20.  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.

22.  David L. Nelson, Michael M. Cox, “Lehninger – Principles of
Biochemistry”, - Fifth edition.
 J. Koolman, K. H. Roehm, “Color Atlas of Biochemistry”, - Secon editon.