signal transduction in the cell and between the cell.

1. INTRACELLULAR SIGNALLING
AND
EXTRACELLULAR SIGNALLING
Prepared by: Sindhoora D
First M pharm.
Department of
Pharmacology
SCP,Manglore
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2. CONTENTS:
• Introduction to cell signalling
• Signal transduction
• Types of signalling pathway
Extracellular signalling
Intracellular signalling
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3. CELL SIGNALLING:
Cell signalling is a type of any communication
process that governs the basic activities of cell
and coordinate all cell action.
Interact with the cellular environment and
neighbouring.
This involves determining function of the cell
within context of the organism as well as the
response of specific cells or group of cell to the
environment.
Communicate using chemical signals.
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4. These chemical signals, which are protein or
other molecules produced by a sending cell are
often secreted from the cell and released into
extracellular space.
Float like a messenger in a bottle over to
neighbouring cell.
When binds to the receptor, it alters the shape or
activity of the receptor, triggering a change inside
the cell.
They are often ligands.
Causes the chain of chemical messenger inside
the cell.
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5. Ultimately ,causes change in the activity of cell.
The extracellular signalling is convert to
intracellular signalling.
Importance of signals:
• Maintenance of homeostasis.
• Control of cell division and cell death
&development and growth.
• Adaptation to environment.
• Hormones and other regulatory mediators.
• Establishment of pathogenesis
&symbiosis,activation of defences.
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6. Signal transduction:
It is a process by which cell receive, propagate
and respond to information from their
environment and each other.
Transmision across the membrane,converting
extracellular to intracellular signals.
Some cases ,additional protein and small
molecule participate in relaying the message
to its ultimate destination in the cell where a
response is evoked.
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8. Steps:
 Biosynthesis and release of the signal.
 Transport of signals to target cell
 Transduction in target cell.
 Alteration of cell growth and metabolism.
 Termination of signals
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9. 16_08_cascades.jpg
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10. Types of signalling pathway:
• Extracellular signalling:
Signalling occurs between the cells ,it may be
a neighbouring cell or a cell in other part of
body.
There are 4 types of signalings:
Contact dependent
Paracrine
Synaptic
endocrine
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12. Contact dependent :
• Bound to the surface of the signalling cells and
influence only cells that contact it.
• The cell makes direct physical contact with a
target cell with the plasma membrane of the
protein.
• Immune response
• Short distance
• Sometimes through a gap junction
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13. Paracrine :
• Signalling molecules released from the signalling
cell to the extracellular space ,targeting cells that
nearby ,thus acting as a local mediator .
• Inflammation during infection ,regulate cell
proliferation
• They act on the cell in the local environment or in
the receptors of own cell it is known as autocrine
signalling
• Cancer cell often produce extracellular signals
that stimulates their own survival and
proliferation
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14. Synaptic :
• the synaptic space.These neurotransmitter are detected by
receptors on the postsynaptic membrane i.e cell meVery
quick, long distance and specific to target cell
• A signal is detected by receptors present on dendrites and
then carried along the axon to a presynaptic
terminal.When the signal reaches the presynaptic
terminal,vesicles containing signalling molecules
(neurotransmitter) fuse with the membrane,releasing the
content into mbrane of target cell,which may be another
neuron or an effector cell.
• Ex:Ach,serotonin,histamine.
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15. Endocrine:
• distance,signall molecules are harmones
• Blood carries the molecule far and
wide,allowing them to act on target cells that
may lie in the body.
• Ex:pancrease secrete insulin,progesterone,
testosterone
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16. Types of receptors:
1. Cell surface receptor
 unable cross the cell membrane , instead
they bind to cell surface receptor.
 Cell surface receptor are also called cell
specific protein or markers because they are
specific to individual cell type.
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17. 2.Intracellular receptor:
• Molecules are hydrophobic, poorly aqueous
soluble.Therefore they are transported in the
bloodstream and extracellular fluid bound to
carrier protien , from which they are
dissociated before entering the target cell.
• Binds to the receptor protein in the cytosol or
in the nucleus.
• Ex:mRNA synthesis in the gene expression
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18. Cell is programmed to respond to
specific signals:
• Cell integrates all this signals to make decision –to
devide, move,differentiate,.Cell requires a specific
combination of extracellular survival factor to
allow the cells to continue living,when deprived
of these signals,the cell undergoes apaptosis.
• Cell proliferation often depends on the
combination of signals that promote both cell
division and survival.
• Differention into non dividing state frequently
requires a different combination of survival
&differention signals that must override any
signal to divide.
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19. 16_06_extracellular_sig.jpg
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20. • A signal molecules has different effects on
different target cell.
• Ex:Ach decreases the action potential firing in
heart pacemaker cell and stimulates the
production of saliva by salivary gland cell even
tough receptor are same on the both the cells.
• In skeleton muscles, Ach causes cell to
contract by binding to a different receptor
protein
• Difference in the intracellular signalling
protein,effector protein and gene that are
activated.
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22. •Intracellular signalling:
• Activation of receptors can trigger the synthesis
of small molecules called second messengers ,
which initiate and coordinates intracellular
signalling pathway.ex:cAMP
• Generates the second messenger or activating
the next signalling or effector protein in the
pathway. Behave like a molecular switches.
• When they receive a signals ,they switch from an
inactive to an active state, untill another process
switches them off and recovering after
transmitting a signal
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23. • Molecular switches consists of protein that are
activated or inactivated by phosphorylation .For
these proteins, the switch is thrown in one
direction by a protein kinase,which is covalently
adds one or more phosphates groups to specific
amino acids on the signalling proteins,in other
direction by a protein phosphate ,which removes
phosphate group.It depends on the balance
between the activities kinase that phosphorylate
it and of the phosphates that dephosphorylate it.
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24. • Protein kinase attach phosphate to the –OH
group of the amino acids in the target protein.
• Two types –serinethreonine kinase,tyrosine
kinase
• This is known as kinase cascades.
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26. • GTP-binding protien switch between an ”on”
state when GTP is bound and an “off” state
when GDP is bound.
• On state they have intrinsic GTPase activity
and shut themselves off by hydrolysing their
bound to GTP to GDP.
• Large Trimeric GTP binding protein help relay
signals from G-protein –coupled receptor that
activate them
• Small monomeric GTPase help relay signals
from many classes of cell surface receptor
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27. Three major class of cell surface
receptor :
1. Ion channel coupled receptor:
• Involved in rapid synaptic signalling between
nerve cells and other electrically excitable target
cells such as nerve and muscle cells.
• Mediated by small no.of neurotransmitter that
transiently open or close an ion channel formed
by the protein to which they bind ,briefly
changing the ion permeability of the plasma
membrane and thereby changing the excitability
of the postsynaptic target cells
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28. 2.G-protein coupled receptor:
 Indirectly regulating the activity of a separate
plasma membrane bound target
protein,which is generally enzyme or ion
channel.
 Trimeric GTP binding protein mediates
 Change the concentration of one or more
small molecules(enzyme),change the ion
permeability(ion)
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29. 3.Enzyme coupled receptors:
• Function as a enzyme or associates directly
with enzyme that they activate.
• They have ligand binding site outside the cell
and their catalytic or enzyme binding site
inside.
• Heterogeneous in structure compared with
other
• Protein kinase or associated with protein
kinase
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30. 16_18_Gprot_subunit.jpg
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31. Some regulate ion channels
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33. Reference
1. Molecular cell biology, seventh edition,
Lodish ,berk kaiser,amon
2. Molecular biology of THE CELL ,sixth edition
,Bruse albert,Alexander Johnson ,Julian Lewis
3. The cell a molecular approach ,Fifth
edition,Geoffrey M.Cooper,Robert
E.Hausman
4. www.slide share .com
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