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Topic : CELL SIGNALLING
Mohammad Vikas Ashraf
Date : 1st October 2016, Saturday
CONTENTS
 General principles of cell signaling
 Types of cell signaling
 Signaling molecules
 Signal transduction
 Cell surface receptors
CELL SIGNALING
 Defined as the transfer of information from one cell to another
in order to communicate and to carry out the functions they
are specialized for.
 Typically a particular type of molecule(signal) is produced by
one cell –The signaling cell-and detected by another-The
target cell by means of a molecule that recieves the signal,and
is known as a Receptor protein.
TYPES OF SIGNALING
 ENDOCRINE SIGNALING: It
broadcast the signal over the whole
body by secreting it in bloodstream.
 PARACRINE : Are released by cells
into the extracellular medium, and
act as local mediators.
 NEURONAL/synaptic: Transmitted
along axons to remote target cells
via neurotransmitters.
 CONTACT-DEPENDENT
SIGNALING: It requires direct
membrane to membrane contact
between cells.
CELLULAR RESPONSE TO SIGNALS
 The signal from a cell-surface
receptor is conveyed to interior of the
cell by various intracellular relay
systems.
 The variance in the relay proteins
makes different cells to respond
differently to the same signal.
 For instance when heart muscles are
exposed to neurotransmitter
acetylcholine, it decreases its
contraction frequency but when a
salivary gland is exposed to the
same signal, it secretes salivary
components.
SIGNALING MOLECULES
o HYDROPHILIC SIGNALING
MOLECULES: The receptors for
these signal molecules lies in the
plasma membrane membrane of
the target cell. As they are too big
or too hydrophilic to cross the
plasma membrane themselves.
o HYDROPHOBIC SIGNAL
MOLECULES: These directly
cross the membrane as they are
highly hydrophobic. Therefore their
receptors lies in the cytosol. E.g:
steroid hormones.
SIGNAL TRANSDUCTION
(SIGNALING CASCADES)
 At successive steps along
this communication
pathway the crucial
points in transmission
occur where the
information is converted
from one form to another.
This process of
conversion is known as
Signal Transduction.
SIGNALING CASCADES
 RELAY PROTEINS: Simply pass the message to
the next signaling component in the cell.
 MESSENGER PROTEINS: Carry the signal from
one part of the cell to another such as from the
cytosol to the nucleus.
 ADAPTOR PROTEINS: Link one signaling protein
to another without themselves conveying a signal.
 AMPLIFIER PROTEINS: Either enzymes or ion
channels, greatly increase the signal they receive.
SIGNALING CASCADES
 TRANSDUCER PROTEINS:Convert the signal in to a
different form.The enzyme that makes cyclic AMP is an
example ‘It both converts the signal as well as amplifies
it.
 BIFURCATION PROTEINS:spread the signal from one
signaling pathway to another.
 INTEGRATOR PROTEINS:Receives signals from
different pathways and integrate them before relaying a
signal onward.
 LATENT GENE REGULATERY PROTEIN:Migrate to
the nucieus to stimulate gene transcription.
SIGNALING PROTEINS
Types of Cell surface receptors
• Ion channel linked
receptors:
• G protein linked
receptors:
• Enzyme linked
receptors:
Ion channel linked receptors
 Also known as transmitter gated ion
channels.
 They transduce a chemical signal
,in the form of a pulse of
neurotransmitter, directly into an
electrical signal.
 When the neurotransmitter binds,
this types of receptor alters its
conformation so as to open or close
a channel for the flow of specific
types of ions across the membrane,
such as-Na+, K+, Ca+, or Cl-.
G-protein linked receptors
 It is a seven-pass
transmembrane receptor
protein.
 Includes rhodopsin and
olfactory receptors in eyes
and smell sensing organs in
vertebrates resp.
 Forms the largest family of
cell surface receptors
 Stimulation of G-protein
linked receptors activates
G-protein subinits.
G-PROTEIN SIGNALING
 G-proteins consist of three sub-units: α,β,γ
 In the unstimulated form both the receptor and the
G- protein are inactive and are probably not in
contact with each other.
 Acctivation of receptor by the ligand/signal molecule
allows the G-protein to bind with the receptor.
 Binding to the activated receptor enables the α-
subunit to exchange its GDP for GTP
SIGNALING THROUGH G-PROTEIN RECEPTORS.
 Phosphorylation of GDP to
GTP causes the G-protein
to break into an activated
α-subunit and β-γ subunit
which diffuses along the
cytosolic membrane untill
they encounter their target
proteins.
Signal termination
 The Alpha subunit has
an intrensic GTP-
hydrolyzing activity and
after a certain time
hydrolyzes the bound
GTP to GDP.
 The α-subunit then
reassociates with the
β,γ complex and the
signal is shut
off/terminated.
Enzyme activation by G-proteins
 The most frequent target
enzymes for G proteins
are:
adenylate cyclase.
 Cyclic AMP,
Phospholipase C
Inositol triphosphate,
Triacylglycerol
 These small intracellular
signaling molecules are
often called second
messengers.
 The cyclic AMP pathway
 Cyclic AMP exerts
these various effects
mainly by activating the
enzyme cyclic-AMP-
dependent protein
kinase (A-Kinase)
ENZYME LINKED RECEPTORS
 Enzyme-linked receptors have been found to mediate
direct, rapid effect on cytoskeleton, controlling the way a
cell moves and changes its shape.
 Like G-protein linked receptors, the enzyme-linked
receptors are transmembrane proteins with their ligand-
binding domains on the outer surface of the plasma
membrane.
 The largest class of enzyme-linked receptors are those
that phosphorylates the tyrosine side chains and are
called as receptor tyrosine kinases.
Cont…
References:
• Essentials of Cell Biology; Bruce Alberts et al; 5th Edition; 2007;
(482-508)
• Cell and Molecular Biology; Gerald Karp; 5th Edition; 2008;
(616-632)
Cell signaling [mva]

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Cell signaling [mva]

  • 1. Topic : CELL SIGNALLING Mohammad Vikas Ashraf Date : 1st October 2016, Saturday
  • 2. CONTENTS  General principles of cell signaling  Types of cell signaling  Signaling molecules  Signal transduction  Cell surface receptors
  • 3. CELL SIGNALING  Defined as the transfer of information from one cell to another in order to communicate and to carry out the functions they are specialized for.  Typically a particular type of molecule(signal) is produced by one cell –The signaling cell-and detected by another-The target cell by means of a molecule that recieves the signal,and is known as a Receptor protein.
  • 4. TYPES OF SIGNALING  ENDOCRINE SIGNALING: It broadcast the signal over the whole body by secreting it in bloodstream.  PARACRINE : Are released by cells into the extracellular medium, and act as local mediators.  NEURONAL/synaptic: Transmitted along axons to remote target cells via neurotransmitters.  CONTACT-DEPENDENT SIGNALING: It requires direct membrane to membrane contact between cells.
  • 5. CELLULAR RESPONSE TO SIGNALS  The signal from a cell-surface receptor is conveyed to interior of the cell by various intracellular relay systems.  The variance in the relay proteins makes different cells to respond differently to the same signal.  For instance when heart muscles are exposed to neurotransmitter acetylcholine, it decreases its contraction frequency but when a salivary gland is exposed to the same signal, it secretes salivary components.
  • 6. SIGNALING MOLECULES o HYDROPHILIC SIGNALING MOLECULES: The receptors for these signal molecules lies in the plasma membrane membrane of the target cell. As they are too big or too hydrophilic to cross the plasma membrane themselves. o HYDROPHOBIC SIGNAL MOLECULES: These directly cross the membrane as they are highly hydrophobic. Therefore their receptors lies in the cytosol. E.g: steroid hormones.
  • 7. SIGNAL TRANSDUCTION (SIGNALING CASCADES)  At successive steps along this communication pathway the crucial points in transmission occur where the information is converted from one form to another. This process of conversion is known as Signal Transduction.
  • 8. SIGNALING CASCADES  RELAY PROTEINS: Simply pass the message to the next signaling component in the cell.  MESSENGER PROTEINS: Carry the signal from one part of the cell to another such as from the cytosol to the nucleus.  ADAPTOR PROTEINS: Link one signaling protein to another without themselves conveying a signal.  AMPLIFIER PROTEINS: Either enzymes or ion channels, greatly increase the signal they receive.
  • 9. SIGNALING CASCADES  TRANSDUCER PROTEINS:Convert the signal in to a different form.The enzyme that makes cyclic AMP is an example ‘It both converts the signal as well as amplifies it.  BIFURCATION PROTEINS:spread the signal from one signaling pathway to another.  INTEGRATOR PROTEINS:Receives signals from different pathways and integrate them before relaying a signal onward.  LATENT GENE REGULATERY PROTEIN:Migrate to the nucieus to stimulate gene transcription.
  • 11. Types of Cell surface receptors • Ion channel linked receptors: • G protein linked receptors: • Enzyme linked receptors:
  • 12. Ion channel linked receptors  Also known as transmitter gated ion channels.  They transduce a chemical signal ,in the form of a pulse of neurotransmitter, directly into an electrical signal.  When the neurotransmitter binds, this types of receptor alters its conformation so as to open or close a channel for the flow of specific types of ions across the membrane, such as-Na+, K+, Ca+, or Cl-.
  • 13. G-protein linked receptors  It is a seven-pass transmembrane receptor protein.  Includes rhodopsin and olfactory receptors in eyes and smell sensing organs in vertebrates resp.  Forms the largest family of cell surface receptors  Stimulation of G-protein linked receptors activates G-protein subinits.
  • 14. G-PROTEIN SIGNALING  G-proteins consist of three sub-units: α,β,γ  In the unstimulated form both the receptor and the G- protein are inactive and are probably not in contact with each other.  Acctivation of receptor by the ligand/signal molecule allows the G-protein to bind with the receptor.  Binding to the activated receptor enables the α- subunit to exchange its GDP for GTP
  • 15. SIGNALING THROUGH G-PROTEIN RECEPTORS.  Phosphorylation of GDP to GTP causes the G-protein to break into an activated α-subunit and β-γ subunit which diffuses along the cytosolic membrane untill they encounter their target proteins.
  • 16. Signal termination  The Alpha subunit has an intrensic GTP- hydrolyzing activity and after a certain time hydrolyzes the bound GTP to GDP.  The α-subunit then reassociates with the β,γ complex and the signal is shut off/terminated.
  • 17. Enzyme activation by G-proteins  The most frequent target enzymes for G proteins are: adenylate cyclase.  Cyclic AMP, Phospholipase C Inositol triphosphate, Triacylglycerol  These small intracellular signaling molecules are often called second messengers.  The cyclic AMP pathway
  • 18.  Cyclic AMP exerts these various effects mainly by activating the enzyme cyclic-AMP- dependent protein kinase (A-Kinase)
  • 19. ENZYME LINKED RECEPTORS  Enzyme-linked receptors have been found to mediate direct, rapid effect on cytoskeleton, controlling the way a cell moves and changes its shape.  Like G-protein linked receptors, the enzyme-linked receptors are transmembrane proteins with their ligand- binding domains on the outer surface of the plasma membrane.  The largest class of enzyme-linked receptors are those that phosphorylates the tyrosine side chains and are called as receptor tyrosine kinases.
  • 21.
  • 22. References: • Essentials of Cell Biology; Bruce Alberts et al; 5th Edition; 2007; (482-508) • Cell and Molecular Biology; Gerald Karp; 5th Edition; 2008; (616-632)