SIGNAL TRANSDUCTION

IN CELLS
 What is signal transduction?
Any process by which cell converts one kind
of signal or stimulus into another.
Signal transduction often involves
a sequence of biochemical reactions
inside the cell, which are carried
out by enzymes and linked
Through second messengers.
TYPES Of Signals
 EXTRACELLULAR
 Signal transduction mainly involves the binding of
extracellular signalling molecules to receptors that face
outwards from the membrane and trigger events inside.
 INTRACELLULAR
 Intracellular signalling molecules in eukaryotic cells include
hetrotrimeric G protein,small GTPases, cyclic nucleotides,
such as cyclic AMP (cAMP) and cyclic GMP(cGMP), calcium
ions,phosphoinositide derivatives,such as Diacylglycerol and
ionisitoltriphosphate and various protein kinases and
phosphatases. some of these are called second messengers.
 INTRACELLULAR
 Within endocrinology, which is the study of
intercellular signaling in animals, intracellular
signaling is subdivided into the following types:
 1) ENDOCRINE
 2) PARACRINE
 3) AUTOCRINE
 4) JUXTACRINE
 5) DIRECT CONTACT SIGNALLING
Direct Contact Signaling
a) Gap junctions
They provide for metabolic cooperation between
adjacent cells and may help maintain hoemeostasis in
connected cells for ion balance. Some signal molecules
may move through gap junctions.
 b)Cell-cell recognition
 Many signal molecules remain bound to surfaces of
signaling cell and influence only cell that contact it
 HORMONES
 They enable signaling between the cells or tissues within
an individual animal or plant.
 Hormones initiated signal transduction takes the
following steps:-
 Biosynthesis of a hormone
 Storage and secretion of a hormone
 Transport of the hormone to the target cell
 Recoginition of the hormone by the hormone receptor
protein, leading to a conformational change
 Relay and amplification of the signal that leads to
defined biochemichal reactions within the target cell. The
reactions of the target cell can in turn, cause a signal to
the hormone producing cell that leads to the down –
regulation of hormone production
Signal Pathways
 Receptor cells on the surface of the plasma
membrane of the cell induce changes in the cell
that give appropriate responses generally some
type of chemical reactions or series of metabolic
reactions.
 The three stages of cell signalling are, therefore,
reception, Transduction and response.
 The series of steps involved is refered to as a
SIGNAL TRANSDUCTION PATHWAY.
 There are variety of methods for signaling
 The stages of chemical cell signalling
1) RECEPTION
 The target cell wall must be able to detect that a signal is
“arriving”.
 This requires a chemical binding to a receptor molecule (
protein), specialised for different functions. Most receptor
molecules are found on the cell surface, but there also
intracellular receptors.
 2) TRANSDUCTION – Initiating the Intracellular Signal
 The receptor molecules binds to the signal molecule in a method
that brings about a change in the receptor molecule when a
conformational change).The change effectively translates(or
transduces) the signal into a form that the target cell can
respond.
 3)RESPONSE:- The cell makes an appropriate response to the
signal. A signal can activate enzymatic activaty, genetic
transcription, movement of cytoskeltal components, or other
cell activates.
There are three main families of cell surface
receptors, each of which transduces
extracellular signal in a different way
G-Protein- Linked Receptors
 Largest family of cell-surface receptors.
 G-proteins are Guanine-nucleotide binding
proteins

 STRUCTURE OF TRANSMEMBRANE a-He

ROLE OF G- protein inSIGNAL TRANSDUCTION
 Trimeric G-Protein disassemble to RELAY SIGNALS
From G –Protein Linked Receptors
G Protein Signal By regulating the
Production of cyclic AMP
 Many extracellular signal molecules work by
increasing cyclic Amp content and they do so by
increasing the activity of adenylyl cyclase rather
then decreasing the activity of phosphodiesterase
 All receptors act via cyclic Amp are coupled to a
stimulatory G protein (Gs) which activates adenylyl
cyclase rather than decreasing cyclic AMP content
 The time during which the a-subunit and by complex
 Remain apart and active is usually short, and it depends ,on
how quickly the a-subunit hydrolyses its bound GTP.
 An isolated a-subunit is an insufficient GTPase, and left to its
own devices, the subunit hydrolyzes its bound GTPase,and,
left to its own devices, the subunit would inactivate only after
several minutes.
 It activation is usually reversed much faster than
this,however, because the GTPase activity of the a- subunit is
greatly enhanced by the binding of a second protein which can
be either its target protein or a specific modulator known as a
regulator of G protein signaling (RGS)
Cyclic –AMP dependent Protein kinase(PKA)
Mediates Most of the Effects of cyclic AMP:-
G Proteins Activate the Inosital Phospholipid
Signaling Pathway
by Activating Phospholipase C-ß:-
 Many G- Protein – Linked receptors exert their effects
mainly via G PROTEINS that activate the plasma
membrane- bound
 enzyme phospholipase C-ß
 The phosphoinositides-P1(4)P and P1(4,5)P2- are
produced by the phosphorylation of
phosphatidyinositol(P1)P, respectively.
 Receptors that operate through this inositol
phospholipid signaling pathway mainly activates a G
PROTEIN called Gq,which in turn activities
phospholipase C-ß, in much the same way that Gs
activates adenylyl cyclase.
 The activated phospholipase cleavage generate two
products:
Inositol 1,4,5- triphosphate and Diacylglycerol.
At this step,the signaling pathway splits into two
branches
 Inositol 1,4,5- triphosphate(IP3) diffuses through the
cystol and releases Ca2+ from the endoplasmic reticulum
by binding to and opening IP3 –gated Ca2+ To escape
into the cystol.
 The large electrochemichal gradient for Ca2+ across the
membrane causes Ca2+ across this membrane causes
ca2+ to escape into he cystol.
 Diacylglycerol remains embedded in the membrane
,where it has two protein signaling roles.
 First, it can be further cleaved to release arachidonic
acid, which can be used in the synthesis of other small
lipid messengers called eicasanoids.
Protein phosporylation and kinase
cascade mechanism:
 The important pathways are;-
 The Ras/Raf/MAP kinase pathway which is
important in cell division, growth and differentiati&
 Ras, which is a proto-oncogene product, functions like a G-
Protein and conveys the signal (by GDP/GTP exchange)
from the SH2 –domain protein Grb, which is phosporylated
by the receptor tyrosine kinase.
 Activation of Ras,in turn , activates Raf, which is the first
of a sequence of serine/theonine kinases,each of which
phosphorylates and activates,the next in line.
 The last of these, MAP( Mitogen –Activated
Protein) kinase, phosphorylates one ore more
transcription factors that initiate gene expression,
resulting in a variety of cellular responses, incuding
cell division.
 The jak/stat pathway, which is activated by many cytokinesis
and which controls the synthesis and release of many
inflammatory meditators
 Dimerisation of these receptors occurs when the cytokine binds,
and this attracts a cytosolic tyrosine kinase unit(jak)to
associate with,and phosphorylate, the receptor dimer.
 Jaks belong to a family of proteins.
 Among the targets for phosphorylation by jak are a family of
transcripton factors(Stats)
 These are SH-2 domain proteins that bind to the
phosphotyrosine groups on the receptor-jak complex,and are
themselves phosphorylated
 Thus activated, Stat migrates to the nucleus and activates gene
expression.
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