3. Receptors are proteins that binds to a specific signal molecule (ligand) and initiates a response in the target cell.
For examples: Cytokine receptors, growth factor receptors and Fc receptor.
Functions:
• Induce cell growth, division and death.
• Control membrane channels or regulate cell binding.
• Receptors play role in signal transduction, immune therapy and immune responses.
Intracellular receptors are small signal
molecules bind to receptor proteins inside the
target cell—either in the cytosol or in the
nucleus.
Cell-surface receptors are signal
transducers for water-soluble extracellular
signals.
Types:
Receptor
4. Ion-channel-coupled receptors, are involved in rapid synaptic signaling between nerve cells and other
electrically excitable target cells such as nerve and muscle cells .
Functions:
• key components in the cellular response to toxins and venoms.
• Play role in biological processes such as T cell activation and hormone release.
Activation of ion channel coupled receptors
Presynaptic neuron releases neurotransmitter from
vesicles into the synaptic cleft during chemical synapse
communication.
The neurotransmitter binds to receptors located on the
postsynaptic neuron and change the ion permeability
of the plasma membrane.
Conformational change in the protein's structure that
allows ions such as Na, Ca, Mg, and H2 to pass
through.
Figure: Mechanism of ion channel coupled receptors
Receptor Families: Ion-channel-coupled Receptors
5. G-protein-coupled receptors indirectly regulate the activity of a
separate plasma-membrane-bound target protein, which is an enzyme
or an ion channel.
Functions:
• Regulate enzyme activity
• Help to open K+ channels in the plasma membrane.
• Regulation of all human senses: sight, smell, taste
• Regulation of immune system and inflammation
• Nervous system regulation
Activation of G-protein-coupled receptors
The G protein-coupled receptor is activated by an external signal in
the form of a ligand or other signal mediator.
This creates a conformational change in the receptor, causing
activation of a G protein.
G proteins are subsequently inactivated by GTPase activating
proteins, known as RGS proteins.
Figure: G-protein-coupled receptors activation
Receptor Families: G-Protein-coupled Receptors
6. Enzyme-coupled receptors are single-pass transmembrane proteins contain ligand-binding site outside the
cell and their catalytic or enzyme-binding site inside. Enzyme-coupled receptors are heterogeneous in structure
and signaling through growth factors, hormones, cytokines. Example: Tyrosine kinase receptors.
Functions:
Responsible for disorders of cell growth, proliferation, differentiation.
Activation of enzyme-linked receptors
Signaling molecule (ligand) binds to receptors as a form of
dimer.
Activation of many intracellular signaling proteins, leading to
changes in gene transcription and in many cellular functions.
Figure: Activation of enzyme-linked receptors
Receptor Families: Enzyme-coupled Receptors
7. Nuclear receptors consist of a single protein that plieotropically regulate a number of physiological processes
including metabolism, immune function, reproduction, and development.
Figure: Mechanism of nuclear receptor DNA binding and transcription activation.
Receptor Families: Nuclear Receptors
8. Second messenger is a small intracellular signaling molecule that is formed or released for action in response
to an extracellular signal and helps to relay the signal within the cell. Examples include cyclic AMP, cyclic GMP, IP3,
Ca2+, and diacylglycerol.
Function: Second messengers trigger physiological changes at cellular level such as proliferation, differentiation,
migration, survival, apoptosis and depolarization.
Mechanisms of second messenger activation
Epinephrine binds to the α1 GTPase Protein
Coupled Receptor (GPCR) results in conformational
change of the receptor.
The activated α subunit activates phospholipase C
the formation of secondary messengers
diacylglycerol (DAG) and inositol-1,4,5-triphosphate
(IP3).
IP3 binds to calcium pumps on ER, transporting
Ca2+
, another second messenger, into the
cytoplasm.
Ca2+
ultimately binds to many proteins, activating a
cascade of enzymatic pathways. Figure: Mechanisms of second messenger activation
Second Messenger
9. Oncogenes are eukaryotic genes. Proto-oncogenes are genes for normal, physiological proteins in the cell, but that
have the potential to cause cancer if mutated. If these proto-oncogenes are mutated in a way that can cause cancer,
they’re called oncogenes.
Functions:
• Oncogenes can contribute to the abnormal behavior of malignant cells.
• The proteins encoded by proto-oncogenes regulate normal cell proliferation
Figure: Activation mechanisms of proto oncogenes
Activation mechanisms of Proto-Oncogenes
(1) Translocation or Transposition:
-Gene moved to new locus, under new control
-New Promoter
-Normal growth-stimulating protein in excess
(2) Gene Amplification:
-multiple copies of the gene
-Normal growth
-stimulating protein in excess
(3) Point Mutations within the gene (Activating)
-Oncogene
-Hyperactive or degradation-resistant protein
Oncogenes
10. Tumor suppressor genes inhibits cell proliferation and tumor development. The first tumor suppressor gene
was identified by studies of retinoblastoma, a rare childhood eye tumor.
Functions:
• Inhibit the same cell regulatory pathways.
• Encode transcriptional regulatory proteins.
Role of p53 a tumor suppressor gene
The p53 protein is a cellular stress sensor. In
response to Hyper proliferative signals, DNA
damage, hypoxia, nutrient deficiency, and
various other stresses, the p53 levels in the
cell rise. As indicated, this may either arrest
cell cycling in a way that allows the cell to
adjust and survive, trigger cell suicide by
apoptosis, or cause cell “senescence”—an
irreversible cell-cycle arrest that stops
damaged cells from dividing.
Figure: Role of p53 a tumor suppressor gene
Tumor suppressor genes
11. Significance of apoptosis:
• Apoptosis removes cells during development
• Eliminates potentially cancerous and virus-infected cells
• Maintains balance in the body
Figure: Mechanisms of apoptosis
Programmed cell death or Apoptosis is a form of programmed cell death that occurs in multicellular
organisms.
Programmed cell death
12. Cell signaling transduction is the process in which information
carried by extracellular messenger molecules is translated into
changes that occur inside a cell.
Molecules involved in Cell Signaling Transduction
Extracellular messenger molecules: growth factor receptors
Transcription factors: Raf-1,Ras etc.
Second messengers: cyclic AMP, cyclic GMP, IP3, Ca2+.
Figure: Molecular mechanism of Signal transduction pathway
Molecular mechanism of signal transduction:
1. Reception: The signal molecule such as estrogens and
other steroid hormones usually binds to a receptor protein
that is embedded in the plasma membrane of the target
cell.
2. Transduction: The receptor activates one or more
intracellular signaling pathways, involving a series of
signaling proteins.
3. Response: Finally, one or more of the intracellular signaling
proteins alters the activity of effector proteins and thereby
the behavior of the cell.
Cell Signaling Transduction
