3. Trans-
membrane
signaling
Trans-membrane signaling processes involve the recognition
and binding of an extracellular signal by an integral membrane
receptor protein and the generation of intracellular signals by
one or more effector proteins.
4. Target cells in body
There are four types of target cells in the body:
Receptor
Ion channel
Carrier molecule
Enzyme
• The most useable target is enzyme
5. Receptor
We mainly discuss trans-membrane signaling with reference to
receptor.
Receptor is a sensing element in the
system of chemical communication
where co-ordinate various functions
cell.
There are four types of receptors:
1. Ligand gated ion channel
2. G-protein coupled receptor
3. Kinase receptor
4. Nuclear receptor
6.
7. RECEPTOR ACTION
Intracellular receptor
In this receptor are
present inside the cell (in
the nucleus).
Regulatory molecule
cross the plasma
membrane to inside
receptor.
These receptor directly
stimulated by regulatory
molecule and shows its
action.
Cell surface receptor
In this receptor are
present at plasma
membrane.
Regulatory molecule can’t
cross plasma membrane.
These receptor shows
action with help of second
messenger e.g cyclic
AMP.
8. Ligand gated ion channel
Ligand-gated ion channels (LGICs) are a group
of transmembrane ion channel proteins which open to allow
ions such as Na+, K+, Ca2+, or Cl− to pass through the
membrane in response to the binding of a
chemical messenger(ligand).
Example
9. Mechanism of action of
ion channel receptor
• Channel closed untill ligand bind to receptor
• After binding the ligand to receptor, a series of reaction is
start which ultimately shows the response and open the
ion channel.
10. G- PROTEIN COUPLED
RECEPTOR
These constitute a large protein family of receptors that
sense molecules outside thecell and activate inside signal
transduction pathways and, ultimately, cellular responses
called G-protein coupled receptor.
11. Mechanism of G-protein
coupled receptor action
• When the regulatory molecule attaches to its receptor
,the a-subunit releases GDP and binds GTP this allows
the a-subunit to dissociate from the βγ subunits.
• Either the α subunit or the βγ complex moves through
the membrane and binds to the effector protein (an
enzyme or ion channel).
• The α subunit splits GTP into GDP and Pi, causing the α
and βγ subunits to reaggregate and bind to the
unstimulated receptor once more.
13. Kinase - linked receptor
A family of receptors with a similar structure. They each
have a tyrosine kinase domain (which phosphorylates
proteins on tyrosine residues), a hormone binding domain,
and a carboxyl terminal segment with multiple tyrosines for
autophosphorylation.
14. kinase linked receptor
structure
Ligand gated binding domain
Extracellular to allow easy access for ligands.
Strong affinity for specific ligands - allows different
ligands that bind to the same receptor to evoke particular
cellular responses.
Transmembrane domain
Contains a series of hydrophobic amino acids.
Cytosolic "active" enzyme domain
Either intrinsic to the receptor or tightly bound via the
cytosolic domain.
The majority are kinases; they phosphorylate specific
threonine, serine, and tyrosine amino acid residues.
15. Mechanism of kinase
linked receptor action
• Ligands are released into the extracellular space upon
binding to their Receptor specific interactions cause a
conformational change within the catalytic domain.
• This Activates the connected enzyme, phosphorylation
generates Tethering sites.
• where Intracellular effector proteins bind these further
relay the signal to the Nucleus resulting in changes
in Gene expression.
16. Example of kinase linked
receptor
Receptor for insulin
• The insulin receptor consists of two parts, each containing a
beta polypeptide chain that spans the membrane, and an
alpha chain that contains the insulin-binding site.
• When two insulin molecules bind to the receptor, the two parts
of the receptor phosphorylate each other.
• This greatly increases the tyrosine kinase activity of the
receptor.
• The activated receptor tyrosine kinase then phosphorylates a
variety of “signal molecules” that produce a cascade of effects
in the target cell.
18. Nuclear receptor
Nuclear receptors are ligand-activated transcription
factors that bind nonpolar regulatory molecules. Because
ligands are nonpolar, they can just diffuse across the
plasma membrane.
19. Nuclear receptor structure
All the nuclear receptors contain three important domains:
1. A transcriptional regulation domain
2. A DNA binding domain
3. A ligand binding domain
20. Mechanism of nuclear
receptor action
• In the absence of ligand, an inhibitory complex
associates with the ligand-binding domain. Ligand
binding causes a conformational change so that the
inhibitory complex (red) dissociates.
• This allows the receptor to bind to DNA, and associate
with the co-regulator protein complex a group of proteins
that regulate gene transcription.
• Genes that are regulated by nuclear receptors contain
particular DNA sequences (response elements) in their
promoters, where the nuclear receptor binds.
• In this way they show the specific response.
