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Manifestation of Novel Social Challenges of the European Union
in the Teaching Material of
Medical Biotechnology Master’s Programmes
at the University of Pécs and at the University of Debrecen
Identification number: TÁMOP-4.1.2-08/1/A-2009-0011
Manifestation of Novel Social Challenges of the European Union
in the Teaching Material of
Medical Biotechnology Master’s Programmes
at the University of Pécs and at the University of Debrecen
Identification number: TÁMOP-4.1.2-08/1/A-2009-0011
Tímea Berki and Ferenc Boldizsár
Signal transduction
INTRODUCTION
PART 1
TÁMOP-4.1.2-08/1/A-2009-0011
History
4 000
Number of
papers published
3 500
3 000
2 500
2 000
1 500
1 000
500
0
1977
1982
1987
1992
1997
2002
2007
Year
• The earliest scientific paper recorded in the MEDLINE database as containing the specific
term signal transduction within its text was published in 1972.
• Research papers directly addressing signal transduction processes began to appear in
large numbers in the scientific literature in the late 1980s and early 1990s.
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Signal transduction
• Signal transduction comes from the verb to
'transduce' meaning to 'lead across'
• In biology signal transduction is the process by
which an extracellular signaling molecule activates
a membrane receptor that in turn alters intracellular
molecules to create a response
• Sensing of both the external and internal
environments at the cellular level relies on signal
transduction
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Cell communication pathways
The cells that are communicating might be close to
each other or far apart:
• Local regulator: cytokines, chemokines
• Neurotransmission: Acetylcholine
• Hormone: steroid and peptide
Cells can also communicate through direct contact:
• Through a cell junction that allows cytoplasmic
continuity
• Adhesion molecules
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Cell communication pathways
Cytokine
producing cell
Inducing stimulus
Target cell
Autocrine action
Cytokine
gene
Cytokine
producing cell
Cytokine producing cell
Paracrine action
Cytokine
Nearby cell
Receptor
Endocrine action
Signal
Gene
activation
Target cell
Circulation
Distant cell
Biological effects
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Mechanisms of cytokine action
Cytokine producing cell
Target cell
Effect
Starting a cascade
Activation
Proliferation
Differentiation
Pleiotropy
A cytokine induces different
effects on different target cells
Activated Th cells
B cell
Proliferation
IL-4
Activated Th cells
INF-g
Thymocyte
Proliferation
Mast cell
Redundancy
The action of more cytokine on
the target cell is similar
Macrophage
IL-2
IL-4
IL-5
Proliferation
Activated Th cells
IL-12
B cell
Synergy
The effect of two cytokines is
stronger than their additive
effects
IL-4
+
IL-5
Activated Th cells
Induces class switch to IgE
B cell
Antagonism
INF-g
One cytokine inhibits the effects
of another cytokine
IL-4
Activated Th cells
Blocks class switch to IgE
induced by IL-4
Activated Th cells
B cell
INF-g, TNF, IL-2 and
other cytokines
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Extracellular signaling molecules
•
•
•
•
•
•
Hormones (e.g., melatonin)
Growth factors (e.g., epidermal growth factor)
Extracellular matrix components (e.g., fibronectin)
Cytokines (e.g., interferon-g)
Chemokines (e.g., RANTES)
Neurotransmitters (e.g., acetylcholine, neuropeptides:
endorphin, small molecules: serotonine, dopamine)
• Neurotrophins (e.g., nerve growth factor)
• Active oxygen species and other electronically-activated
compounds
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Three stages of cell signaling
Reception
• Binding of messengers (ligand) to the receptors
• Receptor activation, changes in conformation, triggers a cascade
Transduction
• Activation of other proteins through protein phosphorylation:
– Protein kinase
– Protein phosphatase
• Second messengers:
– Cyclic AMP
– Calcium ions/Inositol Triphosphate
Response
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Characteristics of the response
• Eventually, the signal creates a change in the cell, either in
the expression of the DNA in the nucleus or in the activity of
enzymes in the cytoplasm, rearrenging the cytoskeleton etc.
• These processes can take milliseconds (for ion flux),
minutes (for protein- and lipid-mediated kinase cascades),
hours, or days (for gene expression).
• There is usually an amplification of the signal - one hormone
can elicit the response of over 108 molecules
• Many disease processes, such as diabetes, heart disease,
autoimmunity, and cancer arise from defects in signal
transduction pathways, further highlighting the critical
importance of signal transduction to biology, as well as
medicine.
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Main types of receptors
Apolar signal
Polar signal
Outside of cell
Cell membrane
Cytoplasm
Membrane bound
receptor
Receptor
Inside of cell
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Types of cell-surface receptors
• Ligand-gated ion channels: e.g. acetylcholine receptor
• G-protein-linked receptors: guanyl nucleotide binding
proteins (G proteins) act as molecular switches; active when
GTP is bound, inactive with GDP due to action of intrinsic
GTPase – muscarinic AchR
• Enzyme-linked receptors: e.g. insulin receptor, T cell
receptor
• Integrins
• Toll-like receptors
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Ligand-gated ion channels
Ions
Signal
molecule
Plasma membrane
Cytoplasm
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7-Transmembrane receptors
Signal molecule
a
b
g
GDP
G-protein
Enzyme
a
b
g
a
Enzyme
GTP
Activated G-protein
Enzyme
GTP
b
g
Activated enzyme
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Mechanism of neurotransmission
• Synaptic vesicles contain a neurotransmitter (NT) and
release it when their membranes fuse with the outer cell
membrane
• Neurotransmitter molecules cross the synaptic cleft and bind
to receptors known as ligand-gated ion channels (LGICs)
and G-protein–coupled receptors (GPCRs) on the
postsynaptic neuron
• GPCRs on the presynaptic neuron’s axon terminal alter the
function of voltage-gated ion channels and modulate
neurotransmitter release
• Neurotransmitter transporters remove neurotransmitter
molecules from the synaptic cleft so that they can be
repackaged into vesicles
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Synapse between two neurons neurotransmission
Presynaptic neuron
(axon terminal)
Synaptic vesicles
NT transporter
Voltage-gated
sodium channel
+
Neurotransmitter molecule
Postsynaptic neuron
Ligand-gated ion
channel
(direct excitation
or inhibition)
GPCR
(modulatory)
+
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Two types of enzyme receptors
Dimer of signal molecule
Inactive
catalytic
domain
Active catalytic
domain
Signal molecule
Enzyme
Activated enzyme