Cell Signaling
Process where cell communicate with other cells & its external environment through
extracellular messenger molecules
Why they communicate?
- For every signal coming to the
For every stimuli there is a response
carry on signal to target cell
Why cell communicate
coordnate myriad activities
monitor external environment
one cellcomplete each other
cell
there will be respond (respond stimuli)
- Carry on signal and the response from other cell they need to communicate (cell
signaling process)
- Monitor environmental condition
- Coordinate the myriad activities needed for the organism different cell need to
complete each others
Types of Signal
Type of Signal
Chemical
EX: cell to cell
communciation
Electromagnetic
Signal (Light)
EX: eye (human),
phototaxis
(plant)
Mechanical
Signal (pressure
or touch)
Cell Signaling Process
- Initiated by binding of signal to receptor at plasma membrane
o Binding is specific but not that specific depending on the respond that is
needed
o Binding is reversible bind to receptor when it is needed
Note: one signal can trigger many responds (EX: adrenaline
- Signal can be replaced by inhibitor/antagonist
o EX: antibiotic block signal produced by pathogen
- 2 kinds of receptor
1. membrane plasma (big & polar) signal not come but only trigger
response
2. intracellular (small & non polar) receptor in cell (can be any receptor)
signal come into the cell and trigger response
Method of cell signaling
Autocrine
Direct Contact
Methof of Cell
Signaling
Paracrine
Synaptic
Endorcrine
1) Autocrine
o Cell secrete chemical messenger
that signal the same cell
- EX: apoptosis, cytokine
interleukin-1
2) Direct contact
o Cell signal move though gap
junction
o Recognition membrane protein
have direct contact to each other
o Same molecule as receptor
- EX: skin cells, white blood cells
& glycol-calyx distinguish
healthy & unwanted cell, ovum
& sperm cell
3) Paracrine
o One cell that release signal which affect target cell
o If signal does not react destroyed by extracellular enzyme
o After signal react remaining is removed from the environment
- EX: nerve on muscle, growth factor, development & embryogenesis,
glycolysis pathway
4) Synaptic
o Specialized paracrine at nervous system
- EX: neurotransmitter release at axon (end of the nerve cell) which then
being transverse (diffused) across synapse to target cell (oth. Nerve cell,
receptor cells, neuromuscular)
5) Endocrine
o One release signal that travel through bloodstream to affect cells in a long
distance to target cell
- EX: hormones affect many target cell that are distant from endocrine
gland through the bloodstream
Response that can be triggered
- Signal molecule causes conformation change in receptor molecule receptor react
with responder relay molecule interaction cellular responses
- Signal molecule cause aggregation of receptor protein in plasma membrane
Classes of Membrane Receptor
Ion Gated Channel Receptor
Ckasses of Membrane
Receptor
Protein Kinase Receptor
G-protein Coupled Receptor
1. Ion-Gated Channel Receptor
o
o
o
o
Mostly found as gated protein poles in plasma membrane
Control the entrance & exit (flow) of component Ca2+, NO, etc.
Gate may open & close as response to signal
EXAMPLE:
- Muscle contraction Ca2+ is needed for myosin & actin but the muscle
must open the ion-gated channel
- Nerve transmission relay info from one sense to another
2. Protein Kinase Receptor
o Activated by phosphorylation, deactivated by protein phosphatase
o Common types (name of receptor is based on the amino acid that build the
kinase receptor):
- Tyrosine kinase
- Serine kinase
- Threonine kinase
- Tryptophan kinase
o How it works?
1) Signal binds to receptor binding site
2) Two protein kinase receptor (i.e. two tyrosine polypeptide) come
together forming dimer
3) Tyrosine molecule in the receptor is phosphorylated (added (P)) by ADP
ATP (active)
4) Active receptor recognize by relay protein in cell causing series of
reaction that happen simultaneously until it reaches target cell
o Can work as 2 things
- As receptor EX: insulin (glucose glycogen)
- As responder or relay protein Ex: as intermediate messenger to
amplify the signal
o Insulin as an Example of Protein Kinase Receptor
3. G-protein coupled receptor
o Structure:
- Compromised of 7 alpha helix within the membrane which serve as:
Attachment of G-protein in cytoplasm
Attachment of signal molecule in the extracellular site
o How it is activated and used
o Uses of G-protein
- Genetic-gender reproduction
- Neurotransmitter
- Sensory reception
- Embryonic development
- Hormone signaling
o Inhibitory that affect signal receptor
- Cholera toxin
How: blocks GTP GDP hydrolysis that involved in salt & water
balance in intestine to cell as a result cell secrete large amount of
water & electrolytes
- Botula toxin
- Whooping cough toxin
Signal Transduction
- Signal molecule bind to receptor conformational change in receptor molecule
transduce signal to a form that can be responded by the target cell
- 2 Types
o Direct transduction
- Direct signal & receptor interaction cause trigger response from
receptor
o Indirect transduction
- Involve cytoplasmic 2nd messenger that mediate steps in transduction
process
- Protein involved: relay protein
Ex: Protein Kinases
Activate cascade (phosphorylation relay) which amplify &
communicate needed signal until target cell (different protein
trigger different responses)
nd
2 (Secondary) Messenger
- Why it is needed?
o The transduced signal cannot reach the target directly
o To amplify & communicate needed signal until target cell process become
more faster, effective, efficient
cAMP (cyclic Adenosine
Monophosphate)
Types of Secondary
Messenger
IP3 (Inositol 3 Phosphate) &
DAG (Diacylglyserol)
Ca2+ ion
NO (Nitric Oxide)
- 4 types
1. cAMP (cyclic adenosine monophosphate)
- EX: glucagon & epinephrine act as signal to trigger conversion of
glycogen into glucose
2. IP3 (Inositol 3 Phosphate) & DAG (Diacylglyserol)
3. Ca2+ ion
- Activated by IP3 and works with DAG
- Function cell division, muscle contraction, chlorophyll synthesis
- Ca2+ ion (as self-independent)
Activate ion (Ca2+) channel for sperm to enter egg cell
Promotes exocytosis
Activate calcium-binding protein, calmodium activate/inhibit
protein kinase & signal transduction pathway
4. NO (Nitric Oxide)
- Function To relax smooth muscle cells, to dilate blood vessel
- Example
Nitroglycerine in CPR cut all steps in signal transduction pathway
until the activation of guanylyl cylase
Viagra & Cialis prevent hydrolysis of cGMP to GMP to GTP (by
phosphorylation) so blood vessel stay dilated
Signal Amplification
- Process how a signal molecule can affect for a greater response of a higher efficiency
- EXAMPLE: Glucose uptake amplification
Signal Efficiency
- By using SCAFFOLDING PROTEIN (signal cascade)
o Bind to both activated membrane receptor & set of protein kinase
o Enable more rapid transduction with multiple function (that cause different
cellular responses)
o Problem: 1 defect all signal that is being transduced is wrong
- EX: genetic disorder (down syndrome)
Response & Responder
- Responder is a molecule within cell that perform/direct the performance of the
appropriate cell activity
- 2nd messenger the one that response to the signal
o Example of response:
Enzymatic Actiity
Respose
Genetic transcription
Movement of
cytoskeletal
component
activation of DNA
&RNA poly
activation of TFS
Ca2+ in muscle cells
NO in dilating blood vessel
- Enzyme activity synthesis of RNA & DNA polymerase
- Genetic transcription activation of transcription factor
- Movement of cytoskeletal component Ca2+ in muscle cells, NO in
dilating blood vessel
Signal Specificity & Cell Response
- Signaling process is required for:
1. Metabolic activity in cell
2. Cell activity
3. Regulate genetic activity
4. Active transport through membrane via channel protein
- Specific receptor in membranes & relay protein in cytosol determine cellular response
o EX: all cell has the same DNA but not all is active active only when needed
- Variety of receptor protein in cell determine:
1. Which gene is expressed in which cell
2. Whether signal cause activation or inhibition response
Signal Regulation
Rate in which signal is transduced
concentration of
intermediary or
target molecule
How signal is
regulated?
EX: how much NO is
synthesized
control of Ca2+ release from endoplasmic
reticulum which is regulated by ion pumps and
IP3 & DAG
Enzyme PDE
(Phosphodiesterase)
EX: conversion of
cAMP --> AMP to
stop G-protein
activity
Protein Phosphatase
EX: to cause
inactivation of
cascade (protein
kinsae relay)
- Termination of signal & 2nd messenger FUNCTION:
1. Act as a switch of signal transduction pathway on when its needed, off
when its not needed
2. Prepares cell for a new signal
