2. No cell can live in isolation, must interact with
environment
In multicellular organisms, cells must
communicate with each other
Growth involves intricate signaling
Same with Differentiation
Even Metabolism requires signaling
4. Depending upon distance travelled by
signalling molecule
◦ Endocrine
◦ Paracrine
◦ Autocrine
◦ Contact dependent
5. Earl W. Sutherland, discovered how hormone
epinephrine acts on cells, suggested that
cells receiving signals went through three
processes:
◦ Reception of signal
◦ Transduction of signal
◦ Response to signal
7. Highly specific binding of signaling molecule
to its receptor
Binding leads to conformational change in
receptor often initiation of signal
transduction
Most receptors are plasma membrane
proteins
8. Some receptors present in the cytosol or nucleus
Small or hydrophobic chemical messengers can
cross plasma membrane and activate intracellular
receptors
e.g. steroid and thyroid hormones
An activated hormone-receptor complex can act as
a transcription factor
9. EXTRACELLULAR
FLUID
Plasma
membrane
The steroid
hormone testosterone
passes through the
plasma membrane.
Testosterone binds
to a receptor protein
in the cytoplasm,
activating it.
The hormone-
receptor complex
enters the nucleus
and binds to specific
genes.
The bound protein
stimulates the
transcription of
the gene into mRNA.
The mRNA is
translated into a
specific protein.
CYTOPLASM
NUCLEUS
DNA
Hormone
(testosterone)
Receptor
protein
Hormone-
receptor
complex
mRNA
New protein
Intracellular Receptors
10. Water-soluble signaling molecules bind to
receptor proteins present in plasma membrane
Three main types of membrane receptors:
◦ G-protein-linked receptors
◦ Enzyme coupled cell surface receptors
◦ Ion channel receptors
11. Plasma membrane receptor
G-protein acts as an on/off switch
GDP bound to G protein is inactive
13. Receptor tyrosine kinases (RTKs)
A receptor tyrosine kinase can trigger
multiple signal transduction pathways at once
Transfers phosphate groups from high-
energy donor molecules, such as ATP, to
specific substrates – signaling intermediates
14. Signal
molecule
a Helix in the
membrane
Signal-binding site
Tyr
Tyr
Tyr Tyr
Tyr
Tyr
Tyrosines
Receptor tyrosine
kinase proteins
(inactive monomers)CYTOPLASM
Tyr
Tyr
Tyr Tyr
Tyr
Tyr Tyr
Tyr
Tyr Tyr
Tyr
Tyr
Tyr
Tyr
Tyr Tyr
Tyr
Tyr
Activated tyrosine-
kinase regions
(unphosphorylated
dimer)
Signal
molecule
Dimer
Fully activated receptor
tyrosine-kinase
(phosphorylated
dimer)
Tyr
Tyr
Tyr Tyr
Tyr
TyrP
P
P
P
P
PATP 6 ADP
Tyr
Tyr
Tyr Tyr
Tyr
TyrP
P
P
P
P
P
Inactive
relay proteins
Cellular
response 2
Cellular
response 1
Activated relay
proteins
6
15. An ion channel receptor acts as a gated
channel
Upon binding signal molecule allows
specific ions, such as Na+ or Ca2+, to pass
through a receptor channel
17. May involve multiple steps
Helps in amplification & Transmission of a
signal
Provides more opportunities for coordination
and regulation
Molecules that relay a signal from receptor to
response are mostly proteins
18. Extracellular signal molecule that binds to
membrane receptor - First messenger
Second messengers are small, non-protein, water
soluble molecules or ions
Second messengers can readily spread in cell by
diffusion
Second messengers propagate pathways initiated
by G protein-linked receptors and receptor
tyrosine kinases
19. Most widely used second messengers
Discovered by Earl W. Sutherland Jr.
Formed from ATP by Adenylyl Cyclase, in response
to an extracellular signal
Many signal molecules trigger formation of cAMP
cAMP usually activates Protein Kinase A, which
phosphorylates various other downstream proteins
21. Ca2+ is an important second messenger
Cells tightly regulate Ca2+ concentration
A signal may trigger an increase in Ca2+ in cytosol
Pathways leading to the release of Ca2+ involve inositol
triphosphate (IP3) and diacylglycerol (DAG) as
second messengers
22. CYTOSOL
Ca2+Endoplasmic
reticulum (ER)
IP3-gated
calcium channel
IP3 (second
messenger)
DAG
PIP2G-protein-linked
receptor Phospholipase C
G protein
Signal molecule
(first messenger)
EXTRACELLULAR
FLUID
GTP
Ca2+
(second
messenger)
Various
proteins
activated
Cellular
re-
sponses
23. Multi-step signaling pathways have important
benefits:
◦ Amplification of the signal
◦ Contributing to the specificity of the response
◦ Provide many opportunity to regulate the signaling cascade
24. Binding of epinephrine to G-protein-linked receptor (1 molecule)
Reception
Transduction
Inactive G protein
Active G protein (102 molecules)
Inactive adenylyl cyclase
Active adenylyl cyclase (102)
ATP
Cyclic AMP (104)
Inactive protein kinase A
Inactive phosphorylase kinase
Active protein kinase A (104)
Active phosphorylase kinase (105)
Active glycogen phosphorylase (106)
Inactive glycogen phosphorylase
Glycogen
Response
Glucose-1-phosphate
(108 molecules)
Amplification
of the signal
25. Different cell types have different set of proteins
Different protein profile gives each cell type
specificity in detecting and responding to signals
Response of a cell to a signal depends on cell’s
protein set
Pathway branching and “cross-talk” further help
the cells to coordinate and regulate response to
incoming signals
26. Signal
molecule
Receptor
Relay
molecules
Response 1 Response 2 Response 3
Cell B. Pathway branches,
leading to two responses
Cell A. Pathway leads
to a single response
The Specificity of Cell Signaling
Cell C. Cross-talk occurs
between two pathways
Response 4 Response 5
Activation
or inhibition
Cell D. Different receptor
leads to a different response
27. Termination mechanisms are an essential aspect
of cell signaling
A way of regulation and control of cell signaling
When signal molecules leave the receptor, the
receptor reverts to its inactive state
Signal may terminate by dephosphorylation of
signaling intermediates (relay proteins)
28.
29. Regulation of Flagella movement by histidine
kinase – a good example of prokaryote signaling
Also an evidence of evolution of Signaling
mechanism from prokaryote to eukaryote
Clock wise and anticlockwise movement of flagella
regulated by signaling- determines its swimming
pattern
30.
31. Cell signalling is basis of Prokaryote and Eukaryote life
For normal functioning coordination of every signaling
pathway is necessary
Altered signalling pathways may lead to diseases
Defect can be in any component of signalling ultimately
leading to the disease development
Cell signalling has been identified in Cancer,
Cardiovascular diseases, Alzheimer's disease, and many
other disorders
Cell Signalling – an important area of research for drug
discovery
32. Cell signaling - essential for survival of both uni-
and multi- cellular organisms
Involves various components and steps
Smooth progression and tight control is required
for homeostasis
Many diseases result from defects in cell signaling
