Cell signaling involves three main stages - reception, transduction, and response. Reception involves signaling molecules binding to membrane receptors, which leads to conformational changes. Transduction refers to the activation of intracellular signaling pathways through second messengers. Response occurs when downstream effectors are activated, bringing about cellular responses like metabolism, gene expression, and cell differentiation. Precise regulation of cell signaling pathways is essential for normal cell function, and defects can lead to diseases.

1. Cell Biology
Unit 11

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

3.  Signalling molecules
 Receptors
 Signalling intermediates
 Effector proteins

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

6. EXTRACELLULAR
FLUID
Reception
Plasma membrane
Transduction CYTOPLASM
Receptor
Signal
molecule
Relay molecules in a signal transduction
pathway
Response
Activation
of cellular
response
Stages in Cell Signaling

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

12. G-protein-linked receptor

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

16. Signal
molecule
(ligand)
Gate
closed Ions
Ligand-gated
ion channel receptor
Plasma
membrane
Gate closed
Gate open
Cellular
response

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

20. cAMP
ATP
Second
messenger
First messenger
(signal molecule
such as epinephrine)
G-protein-linked
receptor
G protein
Adenylyl
cyclase
Protein
kinase A
Cellular responses
GTP

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)

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

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

33. THE END