The document discusses cell signaling pathways and regulation. It describes different types of cell signaling including autocrine, paracrine, synaptic, endocrine, and juxtacrine signaling. It also discusses various signaling molecules like hormones, neurotransmitters, growth factors, and cytokines. The different types of cell surface receptors and intracellular receptors are described, including G protein-coupled receptors, enzyme-linked receptors, and ion channel receptors. The mechanisms of various cell signaling pathways such as G protein signaling and MAP kinase pathways are summarized. Disorders related to improper cell signaling are also mentioned.

1. REGULATION OF CELL SIGNALING PATHWAYS

2. CONTENTS
 CELL SIGNALING
• AUTOCRINE
• PARACRINE
• SYNAPTIC
• ENDOCRINE
• JUXTACRINE
 TYPES OF SIGNALING MOLECULES
• HORMONES
• NEUROTRANSMITTERS
• GROWTH FACTORS
• CYTOKINES
 TYPES OF RECEPTORS
• GPCR
• ENZYME LINKED RECEPTORS
• ION CHANNEL
• INTRNAL RECEPTORS
 DISORDERS RELATED TO SIGNALING

3. CELL SIGNALING
A signaling cell sends a message and it is
received by a target cell

4. CELL SIGNALING AND SIGNAL
TRANSDUCTION
CELL SIGNALING
• the communication
among different groups
of cells and tissues
• How one group of cell
inform other group of
cell- what to do
SIGNAL
TRANSDUCTION
• it refers to how the
presence of an
extracellular signal can
produce a change in the
intracellular state of the
cell without the initial
signal crossing the
membrane

5.  Cell signaling is a part
of complex system of
communication that
governs basic cellular
activities and
coordinates cell actions.
 The ability of cells to
perceive and correctly
respond to their micro-
environment is the basis
of development, tissue
repair and immunity as
well as normal tissue
homeostasis.
 Errors in the cellular
information processing
are responsible for
diseases such as cancer,
autoimmunity and
diabetes.
 By understanding cell
signaling, diseases may
be treated more
effectively

6. WHY DO CELLS
COMMUNICATE…..?

7. Cells do not behave as selfish entities but rather
tend to form «microsocieties» whose proper
functioning requires a precise coordination of
emission and reception of signals. So cells
communicate because-
Cell to cell signal encourage other cells to divide
and act as a dynamic part of tissue.
Cells need to know whether to live, die or divide
Neurotransmission- nerve cell activate adjacent
nerve cell to transmit the signal
Regulation of metabolism
 Immune response
Sex determination and gonad development

8. CLASSIFICATION OF CELL SIGNALING

9. AUTOCRINE SIGNALING
a cell signals to itself, releasing
a ligand that binds to receptors
on its own surface
Example ---response of immune system to foreign antigens
Certain types of T lymphocytes respond to antigenic stimulation by
synthesizing a growth factor that drives their own proliferation, thereby
increasing the number of responsive T lymphocytes and amplifying the
immune response

10. PARACRINE SIGNALING
Molecules released by one cell acts on neighboring
target cells. This affects the cell in the immediate area
of signaling cell

11. SYNAPTIC SIGNALING
Transfer of signals across synapses between
nerve cells. The small distance between
nerve cells allows the signal to travel
quickly; this enables an immediate response

12. ENDOCRINE SIGNALING
Signaling molecules are secreted
by specialized endocrine cells
and carried through blood
stream to the distant target cells

13. Example- PANCREAS
Alpha cells secrete
glucagon hormone when
there is low
concentration of glucose
in the bloodstream
Beta cells secrete insulin
hormone when there is
high concentration of
glucose in the
bloodstream

14. JUXTACRINE SIGNALING
Also known as contact dependent
signaling in which two adjacent cells
make physical contact in order to
communicate

15. SIGNALING MOLECULES
HORMONES
NEURO
TRANSMITTERS
GROWTH
FACTORS
CYTOKINES

16. HORMONES
• These are the signaling molecules produced by
endocrine glands
• Transported by blood stream to the target cells
• These belong to different classes of chemical
structures- amino acids, peptides, proteins or
steroids
• Examples
Adrenaline (amino acid) – increase pulse rate and
blood pressure
Insulin (peptide) – carbohydrate catabolism
Progesterone (steroid) – preparation of endometrial
layer

17. NEUROTRANSMITTERS
• Also known as chemical messengers.
• Neurotransmitters are released from synaptic
vesicles in synapses into the synaptic cleft,
where they are received by receptors on the
target cells
• These transmit the signal from one neuron to
target neuron. These are synthesized from
amino acids.

18. Acetylcholine- an excitatory neurotransmitter at
the neuromuscular junction in skeletal muscle,
causing the muscle to contract.
Dopamine-this includes regulation of motor
behavior, pleasures related to motivation and also
emotional arousal
Gamma-aminobutyric acid (GABA)- during
anxiety, fear and pain GABA stimulate the
feelings of calm and relaxation
Serotonin- It functions to regulate appetite, sleep,
memory and learning and also temperature, mood
and behavior. Some depressed patients are seen
to have lower concentrations of serotonin in
their brain tissue

19. GROWTH FACTORS
• These are any group of proteins that stimulate the
growth of specific tissues
• These bind to the receptors on cell surface
• These play important role in promoting cellular
differentiation and cell division
• Example
Epidermal growth factor-stimulate the growth
of epithelial cells
Platelet derived growth factors- stimulate the
growth of muscle cells and connective tissues
Nerve growth factors- stimulate the growth of
neuronal cells

20. CYTOKINES
• These are signaling proteins that are extensively used
in immune function
• These are produced by immune cells (lymphocytes)
• Cytokines released from one cell affect the actions of
other cells by binding to receptors on their surface
• Examples
 Interferons- these are proteins that inhibit virus
replication inside the cells
 Interleukins – these regulate the immune and
inflammatory responses. Their functions include
growth, maturation and activation of immune cells

21. TYPES OF RECEPTORS
CELL
SURFFACE
RECEPTORS
INTERNAL
RECEPTORS
G- protein coupled
receptors
Enzyme linked
receptors
Ion channel linked
receptors

22. G- protein coupled receptors
• A large protein family of the receptors
• Detect molecules outside the cell
• Activate internal signal transduction
pathway and ultimately cellular
responses
• Ligands that bind and activate the
receptors are odors, pheromones,
hormones and neurotransmitters

23. STRUCTURE OF GPCR
• N terminal is present outside the cell
• 7 α helix is present on the plasma membrane
• C terminal is present inside the cell

24. STRUCTURE OF G- PROTEIN
• Contains 3 polypeptide subunits α, β and γ
• Guanine nucleotide binding site is present on α
subunit
• G- Proteins are held at plasma membrane by lipid
chains that covalently attached to α and γ subunits

25. Types of G-Proteins
S I
Q
G S
PROTEIN
G I
PROTEIN
G Q
PROTEIN

26. MECHANISM
• Ligand binds to receptor
• Conformational changes in the cytoplasmic loops
• Affinity of the receptor to G-Protein
• Ligand bound receptor forms G- Protein Complex
• Conformational change in α subunit replace GDP
with GTP

27. G α subunit dissociates from the
complex and activate the target
Target releases second messenger )
GTPase hydrolyses the GTP back into GDP which
deactivates the target enzyme

28. SECOND MESSENGER
c AMP pathway
• Ligand binds to the
receptor and activate G
protein
• Activation of enzyme
called Adenylyl Cyclase
• Conversion of ATP into c-
APM
• C-AMP stimulate Protein
Kinase A (PKA)
• PKA shows the cell
response

29. SECOND MESSENGER
IP3/DAG pathway
• Ligand binding to the
receptor and stimulation of
GQ protein
• Activation of phospholipase
c
• Breakdown of PIP2
(phosphatydylinositol bis-
phosphate) into IP3 (inositol
triphosphate) and DAG
(diacyl glycerol)
• IP3 opens the ca2+ channel
of SER
• DAG interact with Protein
Kinase C
• PKC has its role in cellular
growth

30. Physiological roles of G protein
receptors
• Taste : GPCR in taste cells mediate the release
of gustducin in response to bitter and sweet
tasting substance
• Smell : receptors of olfactory epithelium bind
the odorants
• Behavior regulation : receptors in brain bind
several different neurotransmitters including
serotonin, dopamine, GABA and glutamate

31. ENZYME LINKED RECEPTORS
• Protein tyrosine kinases are the enzymes that
phosphorylate specific tyrosine residue
• The kinases are involved in cell regulation,
cell growth and cell division
Different growth factors act as ligand for signal
transduction.
• Vascular-endothelial growth factor (VEGF)
This growth factor promotes new blood vessel
growth, but is also important for maintenance
of endothelial cells in the delicate filtration
membrane of the kidney.
• Neurotrophins promote the differentiation of
neurons.
• Epidermal growth factor (EGF) stimulate
the growth of epithelial cells

32. MECHANISM
• The first step is that ligand binding
causes receptor dimerization: that is, binding
of the ligand brings together two receptors.
• The receptors, which are tyrosine kinases, get
phosphorylated with the help of ATP.
• The phosphotyrosine on the phosphorylated
receptor is a binding site for an adaptor
protein.

34. RAS MAP KINASE PATHWAY
• The most common intracellular pathway triggered
by Receptor Tyrosine Kinase is known as
Mitogen Activated Protein Kinase Pathway
(MAPK)
• MAPK pathway is related to cell division and cell
proliferation
• It gives proteins and enzymes which are required
for cell growth
• Signaling molecules to initiate the pathway- EGF
and PDGF
• Receptors are embedded in the plasma membrane

35. MAP KINASE
PATHWAY
EGF- epidermal growth factor
GRB2- growth factor receptor
bound protein
SOS- son of sevenless

36. All the signaling pathways have
“on” and “off” switch
If MAPK pathway
remains “ON”
continuously then what
will happen…..?

37. Due to RAS mutation RAS
permanently binds with GTP then
cell lose the control on cell division.
Cell will continuously grow and
divide which finally leads to
CANCER

38. ION CHANNEL RECEPTORS
• excitable cells (neurons, muscle cells,
and touch receptor cells)
• all of them use ion channel receptors to
convert chemical or mechanical
messages into electrical signals
• an excitable cell maintains a different
concentration of ions in its cytoplasm
than exists in its extracellular
environment
• concentration differences create a small
electrical potential across the plasma
membrane
• “specialized channels” in the plasma
membrane open and allow rapid ion
movement into or out of the cell

40. ION CHANNELS
UNGATED CHANNEL Provide holes, through which ions can
diffuse across the membrane, they
remain open all the time. Example
ungated K+ and Cl- ion channel
VOLTAGE GATED CHANNEL Open or close in response to change in
the membrane potential. Example Na+
and K+ ion channels
MECHANICALLY GATED
CHANNEL
Include touch sensors in the skin and
vibration sensors in the inner ear
Some hollow organs like bladder and
intestine also
TEMPERATURE GATED
CHANNEL
Found in the sensory neuron in the skin,
channels open with an increase or
decrease in the temperature. This leads
to the sensations of warm and cold
LIGAND GATED CHANNEL These open in response to the binding of a
neurotransmitter
Example skeletal muscle cells

41. VOLTAGE GATED ION CHANNEL
• A class of trans-membrane proteins that form ion
channels that are activated by changes in the
electrical membrane potential near the channel
• The membrane potential alters the conformation
of the channel proteins, regulating their opening
and closing
• Cell membranes are generally impermeable
to ions
• Ions diffuse through the membrane through trans-
membrane protein channels

42. Resting membrane
potential in which there
is +ve charge outside
the cell and –ve charge
inside the cell. This is
called as Polarized
state. Activation gates
of Na+ and K+ ion
channels are closed
When a stimulus reaches
the resting neuron, Na+
channels open and allow
Na+ ions from outside to
the inside of the cell

43. When more Na+ ions
move into the cell, inside
become more +ve and
this state is called as
depolarization of the
cell
Now the K+ channels
open and K+ ions move
from inside to the
outside of the cell to
restore the electrical
balance

44. Now it is opposite to initial polarized membrane,
that is there is more K+ ions outside the membrane
and more Na+ ions inside the membrane. This state
is called as Repolarized state.

45. When the impulse has traveled through the neuron,
the action potential is over and then Na+ and K+ ions
will return to their original sides. This state is called
as Polarized state.

46. LIGAND GATED ION CHANNEL
• Transmembrane ion channel which
opens/close in response to binding of a ligand
• Found in those cells which respond to
neurotransmitters released from nerve cells
Ion gated channel ≠ ligand gated channel
Ion channel involves difference in the membrane
potential

47. MECHANISM
• Presynaptic cell release a neurotransmitter via
exocytosis
• Postsynaptic cell express the receptor on its
surface
• When neurotransmitter bind to the receptor,
ion channel opens
• Ions from outside the cell enter the
postsynaptic cell and produces the response

49. INTERNAL RECEPTORS
• Internal receptors, also known as
intracellular or cytoplasmic receptors
• found in the cytoplasm of the cell
• respond to hydrophobic ligand molecules
that are able to travel across the plasma
membrane.

50. Internal receptor
GPCR

51. MECHANISM
• Being lipids, steroid hormones enter the cell by
simple diffusion across the plasma membrane
• Once inside the cell, ligand binds to the
internal receptor
• The ligand receptors complex move into the
nucleus
• Then bind to the specific regulatory regions of
the chromosomal DNA and promotes initiation
of transcription

52. • Transcription is the process of copying the
information in a cell DNA into a special form
of RNA called as messenger RNA
• m-RNA then moves into the cytoplasm and
associates with ribosomes to link specific
amino acids in correct order and produce
protein

54. RECEPTORS LIGANDS
Steroid hormone
receptors
Oestrogen receptor
Glucocorticoid
receptor
Mineralocorticoid
receptor
Androgen receptor
Progesteron receptor
Estradiol
Cortisol
Aldosterone
Testosterone
Progesterone
Thyroid hormone
receptors
Thyroid hormone
receptors
Triiodothyronine (T3)
Vitamin D receptors Vitamin D receptors Hydroxy-
cholecalciferol

55. BIOLOGICAL FUNCTIONS OF
INTERNAL RECEPTORS
• Regulations of growth and embryonic
development
• Maintenance of phenotype
• Regulation of metabolic processes such as
cholesterol and bile acid metabolism

56. When Cell Communication Goes Wrong
The cells in our bodies are constantly sending out and receiving
signals.
But what if a cell fails to send out a signal at the proper time?
What if a signal doesn't reach its target?
What if a target cell does not respond to a signal, or a cell
responds even though it has not received a signal?
These are just a few ways in which cell
communication can go wrong, resulting in disease.
In fact, most diseases involve at least one
breakdown in cell communication.

57. DISORDERS
• Night Blindness
mutations in G-protein.
It affects the response of
rod cells to light
• Pseudohypoparathyroi
dism -the genetic loss
of G(s) protein, results
in non-responsiveness
to parathyroid hormone

58. • Testotoxicosis- mutation in the
receptor for luteinizing hormone can
over-stimulate G(s) proteins, resulting
in the excessive production of
testosterone
• Adenomas G proteins lose their
ability to hydrolyse GTP through
mutation, resulting in the excessive
secretion of growth hormone and the
increased proliferation of cells

59. ALZHEIMER’S DISEASE
It is chronic neuro-degenerative disease that
usually starts slowly and worsens over time
Symptoms-
Short term memory loss
Mood swings
Loss of motivation
Behavioral issues

60. Causes of Alzheimer
Plaques
Due to gene mutation
clumps of protein
called β amyloid
damage and destroy
the brain cell and
interfere with cell to
cell communication

61. Causes of Alzheimer
Tangles
brain cells depend on
internal support and
transport system to carry the
nutrients throughout their
long extensions.
This requires a normal
functioning proteins called
In Alzheimer, protein
threads twist into tangles
leads to failure of transport
and death of brain cells
tau

62. MULTIPLE SCLEROSIS
• A disease in which the protective wrappings
around nerve cells in the brain and spinal cord
are destroyed.
• Affected nerve cell can no longer transmit
signals from one area of the brain to other area
Muscle weakness
Blurred vision
Depression

64. DIABETES
• Type I and type II diabetes
have very similar
symptoms, but they have
different causes
• People who have type I
diabetes are unable to
produce the insulin signal,
• Those with type II diabetes
do produce insulin.
However, the cells of type II
diabetics have lost the
ability to respond to insulin.
• The end result is the same:
blood sugar levels become
dangerously high

65. BARTTER SYNDROME
• It is an Autosomal
recessive disease
• It is caused by
mutations in the genes
coding for K+ and Ca++
channel subunits
• It causes reduced
potassium and excessive
calcium in the urine
Symptoms
• polyuria
• polydipsia
• dehydration
• vomiting
• growth retardation

66. CONCLUSION
In order to response to changes in their
immediate environment, cells must be able to
receive and process signals that originate outside
their borders.
Individual cells often receive many signals
simultaneously and then they integrate the
information they receive into a unified action
plan
Cells also send out the signals to the other cells
both near and far

67. Once the receptor protein receives a signal, it
undergoes a conformational change, which in
turn launches a series of biochemical
reactions within the cell.
The genes encoding for the proteins in cells
can mutate during the cell growth which can
cause disturbance in cell signaling pathway.
The disturbance can lead to several diseases
like Multiple Sclerosis, Alzheimer disease,
Cancer and many more.

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