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BMED 1101 TEACHING BLOCK A

Intercellular Communication Importance of intercellular

Cell signal transduction communication

Dr V S Neergheen Email: [email protected]

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Cells May Interact Directly with Other Cells Through Intercellular Intercellular communication
Junctions or Through Cell Surface Molecules

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Cell May Interact Indirectly with Other Cells Through Secreted Signal Three Major Components of Signaling are Reception, Transduction, and
That Diffuse to the Target the Response

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Signals Received on the Outside of the Cell May Influence Intracellular

Events such as Gene Transcription Receptors Provide Specificity to Signaling

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Ligand Gated Ion Channel (LGIC)

• A type of receptor located in the plasma
Receptor Type Determines the Intracellular Response to Ligand Binding membrane.
• Ligand gated ion channel is also called an
ionotropic receptor.
• Transmembrane protein complexes that are
opened or closed in response to the binding of a
chemical messenger
(ligand).

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• The receptor possess a ligand-binding domain on the

• Neurotransmitters are the principal ligands that bind outer surface of the cell and a channel-forming
to the receptor. domain that transverses the width of the membrane.
• Most of the receptors are pentamers( 5 subunits) and • The receptor forms therefore an integral part of the
each subunit has 4 transmembrane spanning regions. ion channel.

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Such receptors are located at synapses and convert Examples of LGIC

the chemical signal of presynaptically released
neurotransmitter directly and very quickly into a
postsynaptic electrical signal. Cation permeable Anion permeable
Na+, K+ and Ca2+ Cl-
• Nicotinic acetylcholine • γ-aminobutyric acid-
receptor gated(GABAA receptor)
• Glutamate receptor • Glycine receptor

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Enzyme-linked receptors Classes of enzyme-linked receptors

• Transmembrane receptors 1. Tyrosine-specific receptor protein kinases
• Ligand-binding domain:- on outer surface of plasma membrane 2. Tyrosine kinase associated receptor
• Cytosolic domain:- intrinsic enzyme activity or associates directly with 3. Receptor serine/threonine kinase
an enzyme 4. Transmembrane receptor guanylcyclases
5. Receptor tyrosine phosphatase

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Receptor tyrosine kinase (RTK) Types of RTKs

• They are acted upon by growth factors and hormones.
• E.g. epidermal growth factor(EGF)
• Platelet-derived growth factor(PDGF)
• Fibroblast growth factor(FGF)
• Insulin

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Ras
• Proteins belonging to Ras superfamily of monomeric GTPases.
• Helps to transmit signals from cell surface to other parts of cell e.g.
nucleus
• Ras + GTP = active
• Ras + GDP = inactive
• GEF activate Ras
• GAP inactivates Ras

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3. This activates the tyrosine kinase domain.

How is the signal transmitted? 4. Autophosphorylation causes the assembly of a large
intracellular signalling complex.
1. Signal protein binds to ligand-binding domain, causing the receptors 5. GRB2, with SOS bound to it, binds to the
to form a dimer. phosphorylated tyrosine residues(docking sites) via
2. The receptor chains cross-phosphorylate each other on multiple their SH2 domains.
tyrosine. Process is known as autophosphorylation.

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5. This activates SOS. 10. MAP-KKK (Raf) is phosphorylated to MAP-

6. SOS causes Ras to bind to GTP, activating it. KK(Mek).
7. Activated Ras causes a series of serine/threonine
phosphorylations. 11. MAP-KK then activates MAP-K.(Erk)

12. This kinase cascade causes amplification of the

signal.

13. Activated MAP-K then phosphorylates gene

regulatory proteins and protein kinases.

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THE JAK-STAT SIGNALLING PATHWAY

RTK signalling pathway

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G-Protein
• Guanosine Nucleotide binding protein
• Alfred G. Gilman and Martin Rodbell discovered some
critical roles of these proteins.
• Serve as molecular binary switches.

G-Protein

Monomeric
Small G-Protein
Trimeric (Ras)
α,β,γ subunits e.g. in insulin
signaling

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Epinephrine binding at β-adrenergic receptor One Consequence of Signal Transduction is Amplification of the
Response

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Second Messenger Systems Amplify the Initial Signal and Usually Work
Through a Protein Kinase A Common Second Messenger is cAMP

cAMP is a nucleotide
cAMP activates a protein kinase

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Both cAMP and DAG/IP3 Pathways Work Through G-Protein

DAG and IP3 are Common Second Messengers Intermediates

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Interactions of Different Transduction Pathways Lead to Diversity of

Responses

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Steroids Hormone Receptors Nuclear receptors

Steroid hormone receptors can be found • Steroid receptors of the nuclear receptor family are all
ØThe plasma membrane transcription factors.
ØThe cytosol • Nuclear receptors play key roles in both embryonic
development and adult homeostasis.
ØThe Nucleus of Target cells
• However they are mostly intracellular • They may be classified according to either mechanism
or homology.
receptors(typically cytoplasmic) and initiate signal
transduction for steroid hormones which leads to
changes in gene expression over a time period of
hours to days.
• The best studied steroid hormone receptors are the
members of the nuclear receptor subfamily 3(NR3)
that include receptors for estrogen.

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Structure of nuclear receptors

• Nuclear receptors contains the following domains:
vN-terminal regulatory domain
vDNA Binding domain-Highly conserved domain
containing two zinc fingers that binds to specific
sequences of DNA called hormone response
elements.
vHinge region
vLigand binding domain-Binds to the ligand and in
addition, binds coactivator and corepressor proteins.
vC-terminal domain

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