2. In multicellular organisms there is a variety of signaling molecules
that are secreted or expressed on the cell surface of one cell and
bind to receptors expressed by other cells.
These molecules integrate and coordinate the functions of the cells
that make up the organism.
Cells within multicellular organisms communicate via extracellular
mediators: either through diffusible molecules or by direct cell2cell
contact
Cell Signaling
3. Local and Long-Distance Signaling
Like bacteria or yeast cells, cells in a multicellular organism
usually communicate via chemical messengers targeted for
cells that may or may not be immediately adjacent
eukaryotic cells may communicate by direct contact one type of local signaling.
Both animals and plants have cell junctions that, where present, directly connect
the cytoplasms of adjacent cells
signaling substances dissolved in the cytosol can pass freely between adjacent
cells. Moreover, animal cells may communicate via direct contact between
membrane bound cell surface molecules in a process called cell-cell recognition
4.
5. Messenger molecules are secreted by the signaling cell.
They travel only short distances; such local regulators influence cells
in the nearby region.
One class of local regulators in eukaryotes are growth factors,
consists of compounds that stimulate nearby target cells to grow and
divide.
Numerous cells can simultaneously receive and respond to the
molecules of growth factor produced by a single cell in their vicinity.
This type of local signaling is called paracrine signaling
6. specialized type of local signaling is called synaptic signaling occurs in eukaryotes
An electrical signal along a nerve cell triggers the secretion of neurotransmitter
molecules carrying a chemical signal.
These molecules diffuse across the synapse and triggers a response in the target
cell.
Animals and plants use chemicals called hormones for long distance signaling. In
hormonal signaling in animals, also known as endocrine signaling.
Specialized cells release hormone molecules, which travel via the circulatory
system to other parts of the body, where they reach target cells that can recognize
and respond to the hormones
9. Stage I: Reception is the target cell’s detection of a signaling molecule coming from
outside the cell.
A chemical signal is “detected” when the signaling molecule binds to a receptor
protein located at the cell’s surface or inside the cell.
Stage II: Transduction -The binding of the signaling molecule changes the receptor
protein, initiating the process of transduction.
The transduction stage converts the signal to bring about a specific cellular
response.
Transduction sometimes occurs in a single step but more often requires a sequence
of changes in a series of different molecules—a signal transduction pathway. The
molecules in the pathway are often called relay molecules
THE THREE STAGES OF CELL SIGNALING
10. Stage III : Response: In the third stage of cell signaling, the
transduced signal finally triggers a specific cellular response.
The response may be almost any imaginable cellular activity
such as catalysis by an enzyme or activation of specific genes in
the nucleus.
11. Stage I : Reception
Stage II : Transduction
Stage III : Response
12. Local regulator
diffuses through
extracellular fluid
Target cell
Secretory
vesicle
Electrical signal
along nerve cell
triggers release of
neurotransmitter
Neurotransmitter
diffuses across
synapse
Target cells stimulated
Local signaling (Left: Paracrine, Right: Synaptic)
13. Paracrine signaling communicates with all cells surrounding and
coordinates efforts (e.g. growth factors are released to stimulate
mitosis in all cells near a wound to promote healing)
Synaptic signaling occurs when the signal is directed to only one
neighbor cell (e.g. neurotransmitters pass from one neuron to the
next to send a signal to the brain)
14. Two types voltage-gated ion channels (VGIC) and ligand gated ion
channels (LGIC)
A ligand gated ion channel is a type of membrane receptor containing
a region that can act as a “gate”
When a signaling molecule binds as a ligand to the receptor protein,
the gate opens or closes, allowing or blocking the flow of specific ions,
such as Na+ or Ca2+, through a channel in the receptor.
These proteins bind the ligand at a specific site on their extracellular
sides.
ION CHANNELS
15. Mitogen-activated protein kinase (MAPK) pathways regulate
proliferation and differentiation to apoptosis.
On activation they phosphorylate many proteins, including
transcription factors, cytoskeletal proteins, kinases and other
enzymes, and many influence gene expression, metabolism, cell
division, cell morphology and cell survival.
MAP kinases are found in eukaryotes only
MAP KINASE PATHWAYS
16. It begins with MAP Kinase Kinase Kinase (MAPKKK), a family of
enzymes which in turn activates the second step in the
cascade, the family of MAP Kinase Kinases (MAPKK), which
then activate the MAP Kinases (MAPK) which have the actual
effects of stimulating the transcription of specific genes in the
nucleus, particularly the Immediate Early Genes required for
mitotic division.
17. Each MAPK pathway contains a three-tiered kinase
cascade comprising a MAP kinase kinase kinase
(MAPKKK, MAP3K, MEKK or MKKK), a MAP kinase
kinase (MAPKK, MAP2K, MEK or MKK) and the MAPK.
This three tier module mediates ultrasensitive switch
like responses to stimuli
18. Signal
molecule
Signal-binding site
CYTOPLASM
Tyrosines
Signal
molecule
Helix in the
Membrane
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Dimer
Receptor tyrosine
kinase proteins
(inactive monomers)
P
P
P
P
P
P
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
P
P
P
P
P
P
Cellular
response 1
Inactive
relay proteins
Activated
relay proteins
Cellular
response 2
Activated tyrosine-
kinase regions
(unphosphorylated
dimer)
Fully activated receptor
tyrosine-kinase
(phosphorylated
dimer)
6 ATP 6 ADP
Receptor tyrosine kinases
19. JAK signaling (Just Another Kinase or Janus (Tyr) kinase)
Janus NH(2)-terminal kinase (JNK) is a member of an evolutionarily conserved sub-family of
mitogen-activated protein (MAP) kinases Mediate
cytokines
(interferons,
interleukins)
signals:
Modulate cell
growth,
differentiatio
n, and
immune
response
20. P38 MAP KINASE (MAPK)
p38 MAP kinase (MAPK), is the mammalian orthologue of the yeast HOG
kinase that participates in a signaling cascade controlling cellular
responses to cytokines and stress . Four isoforms of p38 MAPK, p38α, β, γ
and δ (also known as SAPK4) have been identified.
p38 MAPK is activated by a variety of cellular stresses including osmotic
shock, inflammatory cytokines, lipopolysaccharide (LPS), UV light, and
growth factors
On activation it inhibits the activation of MAPKAPK-2 by p38 MAPK and
subsequent phosphorylation
21. RAS is the name given to a family of related proteins found inside
the cells
RAS protein belongs to a small GTPase protien, and are involved
in transmitting signals within cells
RAS signals result in cell growth and division, overactive RAS
signaling can ultimately lead to cancer
Permanently activate RAS are found in 20-25% of all human
tumors and up to 90% in certain pancreatic cancer
22. Ras is a membrane-associated guanine nucleotide binding protein
It activates RTKs (Receptor Tyrosine Kinases), TCR (T-Cell
Receptors) and PMA (Phorbol-12 Myristate-13 Acetate).
Ras signaling affects many cellular functions, which includes cell
proliferation, apoptosis, migration, differentiation.
Ras acts as a binary signal switch
Ras is tightly bound to GDP (Guanosine Diphosphate), which is
exchanged for GTP (Guanosine Triphosphate) upon binding of
extracellular stimuli to cell membrane receptors
23. Phosphatidylinositide 3-kinases (PI 3-kinases or PI3Ks) are a family of enzymes
involved in cellular functions such as cell growth, proliferation, differentiation,
motility, survival.
Play key roles in cardiac growth (PI3Kα),cardiac contractibility and the
function of β-adrenergic receptors (PI3Kγ)
(PI3K),catalyzes the production of phosphatidylinositol-3,4,5-trisphosphate, in
cell survival pathways and regulation of gene expression and cell metabolism;
and cytoskeletal rearrangements.
The PI3K pathway is found in human diseases including diabetes and cancer.
PI 3-KINASES
24.
25. Optical biosensor is an analytical tool for biomolecular interaction analysis.
Biosensor consists of a biological component, a detector element, and a
transducer which associates both biological component is a protein
target(receptor)
Biosensors can be created by attaching one or more fluorescent proteins to a
target protein
sensors, incorporation of a fluorescent tag into the primary amino acid sequence
of a protein or a selected protein domain, has made researchers to track various
components of intracellular signaling networks within the native cellular
environment.
Biosensor
