3. Signal Transduction
It is a process of converting
a extracellular signal into a
response.
The conversion of this signal
is brought out by the
extracellular signaling
molecules known as Ligand.
4. Ligand:-
Substances synthesized and
released by signaling cells
and produce a specific
response only in target cells
that have receptors for the
signaling molecules.
5. The extra cellular signaling
molecule binds with the located
on the cell surface or inside the
cell and in turn the receptor
triggers the biochemical chain of
events in the cells which leads to
Cellular Response.
Cellular response:-
1)Change in gene expression.
2)Cell morphology.
3)Cell movement.
6.
7.
8. Steps involve in extracellular
signaling:-
1) Synthesis of extracellular molecule.
2) Release of the signaling molecule by
the signaling cell.
3) Transport of the signal to the target
cell.
4) Detection of the signal by a specific
receptor protein.
5) A change in cellular metabolism,
function, or development triggered by
the receptor-signal complex .
6) Removal of the signal, which often
terminates the cellular response.
9. Types of Signaling:-
ENDOCRINE SIGNALING :-
Signaling molecules (hormones) act
on target cells distant from their site of
synthesis by cells of endocrine organs.
PARACRINE SIGNALING :-
The signaling molecule
(neurotransmitter) released by a cell
only affect target cells in close
proximity to it.
AUTOCRINE SIGNALING :-
Cells respond to substances (growth
factors) which they themselves release
10. Membrane Receptors:-
In signal transduction the
signaling molecule first
binds to the receptors that
my be present on the
surface of membrane or
inside the cell.
11. Receptor:-
A region of tissue, or a
molecule in a cell
membrane, which responds
specifically to a particular
neurotransmitter, hormone,
antigen, or other substance.
12. Receptor can be intra
cellular or extracellular
1)Intracellular Receptor:-
They are present inside the
cell and upon binding with
ligand triggers the series of
changes. They are
hydrophobic in nature.
13. 2)Extracellular Receptor:-
Cell surface receptor that are
specialized are integral trans
membrane protein that take
part the communication b/t
the cells. Ligand may be
harmone,cytokine,growth
factors etc which binds to the
receptor but don’t move inside
the cell.
14.
15. Based on structural and
functional similarities,
membrane receptors are
mainly divided into 3 classes:-
1)Ion channel linked receptor
2)Enzyme linked receptor.
3)G protein coupled receptor .
16. Receptors
• INTRACELLULAR RECEPTORS :- 1) Cytoplasmic
2)Nuclear receptors
• CELL SURFACE RECEPTORS:-
ION CHANNEL RECEPTOR
(inotropic)
• Ligand gated ion
channels
• Controlled by
neurotransmitters
• Present in neurons
• Eg: Ach cation channel
G -PROTEIN LINKED RECEPTOR
(Metabotropic)
• Act via second
messengers-cAMP, IP3,
DAG , c GMP
ENZYME LINKED RECEPTOR
• Eg:
Protein kinase
Tyrosine kinase
Tyrosine phosphotase
Serine/threonine kinase
Guanylyl cyclase
Histidine kinase
17. Ion channel linked receptors :-
They are ion-channels (including
cation-channels and anion-channels)
Na K Cl Ca themselves and constitute a
large family of multiple
transmembrane proteins. They are
involved in rapid signaling events most
generally found in electrically excitable
cells such as neurons and are also
called ligand-gated ion channels.
Opening and closing of Ion channels
are controlled by neurotransmitters.
18.
19. Enzyme-linked receptors:-
They are either enzymes
themselves, or are directly
associated with the enzymes
that they activate. The majority
of enzyme-lined receptors are
protein kinases, or associate
with protein kinases
20.
21. G-protein coupled receptors
These receptors activate a G protein
ligand binding. G-protein is a trimeric
protein. The 3 subunits are called α、β
and γ. The α subunit can bind
with guanosine diphosphate, GDP. This
causesphosphorylation of the GDP
to guanosine triphosphate, GTP, and
activates the α subunit, which then
dissociates from the β and γ subunits.
The activated α subunit can further
affect intracellular signaling proteins or
target functional proteins directly.
22.
23. Messenger:-
A particular substance that
can carry or transfer an
massage which in terms of
biology may be a
harmone,protein etc
24. Primary Messenger:-
Transmit the signal from
receptor to the enzyme and
activate it to produce
secondary messenger.
Example:
Gα,Gβ
25. Secondary Messenger:-
Secondary messenger are the
intracellular molecule released by the
cell to trigger physiological changes.
After the receptor being activated the
secondary play a vital role in s Transmit
signals in form of either direct cellular
response eg:cAMP, cGMP
Or activate further enzymes to produce
response Eg :IP3,DAG signal
transduction.
29. Cyclic AMP is synthesized from ATP by the
action of the enzyme adenylyl cyclase.
Binding of the hormone to its receptor
activates
G protein which, in turn, activates adenylyl
cyclase.
The resulting rise in cAMP turns on the
appropriate response in the cell by either (or
both):
Changing the molecular activities in the
cytosol, often using Protein Kinase A (PKA)
cAMP-dependent protein kinase that
phosphorylates target proteins;
turning on a new pattern of gene
transcription.
31. Some of the hormones that
achieve their effects through
cAMP as a second
messenger:
1)Adrenaline
2)Glucagon
3)Luteinizing hormone (LH)
32. Cyclic GMP serves as the
second messenger for:-
1) Atrial natriuretic
peptide (ANP)
2)Nitric oxide (NO)
3)The response of the rods
of the retina to light.
33. Inositol trisphosphate (IP3) and
Diacylglycerol (DAG):-
As its name suggests, it
hydrolyzes phospholipids specifically
phosphatidylinositol-4,5-bisphosphate (PIP2)
which is found in the inner layer of the
plasma membrane. Hydrolysis of PIP2 yields
two products:
Diacylglycerol (DAG)
DAG remains in the inner layer of the plasma
membrane. It recruits Protein Kinase C (PKC)
a calcium-dependent kinase that
phosphorylates many other proteins that
bring about the changes in the cell.
34. Inositol Triphosphate IP3:-
As its name suggests,
activation of PKC requires
calcium ions. These are
made available by the action
of the other second
messenger — IP3.
inositol-1,4,5-
trisphosphate (IP3)
35. Peptide and protein hormones like
1)Vasopressin,
2)Thyroid-stimulating hormone.
3)Angiotensin.
4)Neurotransmitters like GABA.
They bind to G protein-coupled
receptors (GPCRs) that activate the
intracellular enzyme
phospholipase C (PLC).
36.
37. Calcium ions (Ca2+):-
As the functions of IP3 and DAG
indicate, calcium ions are also
important intracellular
messengers. In fact, calcium ions
are probably the most widely used
intracellular messengers.
In response to many different
signals, a rise in the concentration
of Ca2+ in the cytosol triggers many
types of events such as:
38. 1)Muscle contraction.
2)Secretion of hormones like insulin.
3)Activation of T cells and B cells when
they bind antigen with their antigen
receptors (TCRs and BCRs respectively).
4)Adhesion of cells to the extracellular
matrix (ECM).
5)Apoptosis.
6)A variety of biochemical changes
mediated by Protein Kinase C (PKC).
39. Getting Ca2+ into (and out of)
the cytosol:-
1) Open in response to a change in
membrane potential, e.g. the
depolarization of an action potential.
2)Skeletal muscle
3)Smooth muscle (These are the channels
blocked by drugs, such as felodipine [Plendil],
used to treat high blood pressure. The influx of
Ca2+ contracts the smooth muscle walls of the
arterioles, raising blood pressure.The drug
block this .
40. 4)When the action potential
reaches the presynaptic terminal,
the influx of Ca2+ triggers the
release of the neurotransmitter.
5)Receptor-operated channels like
G-protein-coupled
receptors (GPCRs). These are not
channels but they trigger a release
of Ca2+ from the endoplasmic
reticulum as described above.
41. Ca2+ ions are returned:-
They return to the ECF by active
transport using an ATP-driven pump
called a Ca2+ ATPase.
3 Na+ ions flowing DOWN their
concentration gradient to pump one
Ca2+ against its gradient and 4 Na+ ions
flowing down to pump 1 Ca2+ and 1
K+ ion up their concentration gradients.
42. Nitric Oxide (NO)
Nitric oxide (NO) acts as a second messenger
because it is a free radical that can diffuse
through the plasma membrane and affect nearby
cells.
It is synthesised from arginine and oxygen by the
NO synthase.
It activates soluble guanylyl cyclase, which when
activated produces another second messenger,
cGMP.
It is toxic in high concentrations , but is the cause
of many other functions like relaxation of blood
vessels, apoptosis etc
45. The last step but not least of
the signal transduction is
gene expression.
Gene:-
A gene is the sequence of
nucleotides in DNA
encoding one polypeptide
chain or one mRNA
molecule.
46. Gene Structure
Eukaryotic gene structure: Most
eukaryotic genes in contrast to typical
bacterial genes , The coding sequence
(Exons) are interrupted by noncoding
DNA (Introns).
Exons:Expressed sequence.
Introns:Intervening or un expressed
sequence
47. Classification of gene with
respect to their Expression:
Constitutive ( house keeping) genes:
1- Are expressed at a fixed rate,
irrespective to the cell condition.
2- Their structure is simpler
Controllable genes:
1- Are expressed only as needed.
Their amount may increase or
decrease with respect to their basal
level in different condition.
2- Their structure is relatively
complicated with some response
elements
48. Gene Expression:-
It is the process by which
information from a gene is
used in the synthesis of a
functional gene product.
These products are often
proteins, but in non-protein
coding genes such as rRNA
genes or tRNA genes, the
product is a functional RNA
49. Gene expression is carried
out in 2 steps:
1) Transcription.
2) Translation.
50. Regulation of Gene Expression
Promoters
The region necessary to initiate
transcription.
Consists of short nucleotide sequence
that serve as the recognition point for
binding of RNA polymerase.
Located adjacent to the genes they
regulate.
51. There are significant differences in
number , orientation and distance
between promoters in different
genes.
Promoters for RNA polymeraseII
include:
TATA
CAAT
GC
52. Enhancers
DNA sequences interact with
regulatory proteins & increase
the efficiency of initiation and
transcription and thus increase
its rate.
53. Enhancers:
1)Large up to several
hundred bp long).
2)Large Tissue- specific
stimulate transcription only
in certain tissues
54. Transcription Factor
They are proteins essential for
initiation of the transcription, but
they are not part of RNA polymerase
molecule that carry out the
transcription process.
55. Functions:
Each RNA polymerase requires a
number of transcription factors which
help in:
1. Binding of the enzyme to DNA
template.
2. Initiation and maintenance of
transcription.
3. Control the rate of gene expression
56. 1) Special TFs:
Involved in regulation of heat, light,
and hormone inducible genes.
They bind to:
a. enhancers.
b. Basal TFs.
c. RNA polymerase that bind to the
gene promoter.
Thus special TFs can regulate the
transcriptional activity of the gene.
57. 1.Positive regulation:
When the expression of genetic is
quantitatively increased by the
presence of specific regulatory
element is known as positive
regulation.
Element modulating positive
regulation is known as activator or
positive regulator
58. 2.Negative regulation
When the expression of genetic
information diminished by the
presence of specific regulatory
element.
The element or molecule mediating
the negative regulation is said to be
repressor.
61. OPERON in gene regulation of
prokaryotes
Definition: A fewgenes that
are controlled collectively by one
promoter
Its structure: Each Operon is
consisted of few structural genes(
cistrons) and
some cis-acting element such as
promoter (P) and operator (O)
72. Eukaryotic gene regulation at
several levels
1.Transcriptional control.
2.RNAprocessing control.
3.RNA transport /localisation
control.
4.Translation control.
5.mRNAdegradation control.
6.Protein activator control.
73.
74.
75.
76.
77. Research Article
Female resistance to
pneumonia identifies
lung macrophage nitric
oxide synthase-3 as a
therapeutic target
78. Abstract
To identify new approaches to enhance
innate immunity to bacterial pneumonia,
we investigated the natural experiment of
gender differences in resistance to
infections. Female and estrogen-treated
male mice show greater resistance to
pneumococcal pneumonia, seen as
greater bacterial clearance, diminished
lung inflammation, and better survival.
79. Abstract
In vitro, lung macrophages from female mice
and humans show better killing of ingested
bacteria. Inhibitors and genetically altered
mice identify a critical role for estrogen-mediated
activation of lung macrophage nitric
oxide synthase-3 (NOS3). Epidemiologic data
show decreased hospitalization for pneumonia
in women receiving estrogen or statins (known
to activate NOS3).
80. Pharmacologic targeting of NOS3 with
statins or another small-molecule
compound (AVE3085) enhanced
macrophage bacterial killing, improved
bacterial clearance, and increased host
survival in both primary and secondary
(post-influenza) pneumonia. The data
identify a novel mechanism for host
defense via NOS3 and suggest a potential
therapeutic strategy to reduce secondary
bacterial pneumonia after influenza
81. References
Guyton & Hall text book of medical
physiology.
McGraw Hill physiology
Kuby Immunology
Immunology at a glance( J.H.L
Playfair & B.M Chain
Essentials of medical physiology
(TAYPEE)
