Cellular signaling and signal transduction play important roles in coordinating cells and processes in the human body. Signals are transmitted via direct cell contact, hormones, growth factors, and ligands that bind to cell surface receptors. There are different modes of cell communication including autocrine, endocrine, paracrine, and synaptic signaling. Key components of signal transduction include G-protein coupled receptors, receptors with kinase activity, and various intracellular and extracellular receptors. Diseases can arise from defects in these signaling pathways, such as night blindness from mutations in G-protein subunits or excessive hormone production from mutations in receptors.

1. Cellular Signaling
Mechanism
Presented by:
Masoom Raza
Analytical methodology
PhD 1st Year (Life Sciences)

2. INTRODUCTION
In human body, numerous processes are required for coordinating individual cells to support the
body as a whole.
At the cellular level, Sensing of environments and cell communication for coordination relies on
signal transduction; modeling signal transduction systems as self-organizing allows one to explain how
equilibria are maintained.
Many disease processes, such as diabetes and heart disease arise from defects or dysregulations in
these pathways, highlighting the importance of these processes in human biology and medicine.

3. Cell communication occurs through chemical signals and cellular receptors by either the
1) direct contact of molecules on two cells surfaces or the
2) release of a "chemical signal" recognized by another cell (near or far).
Hormones are carried by the circulatory systems to many sites.
Growth factors are released to act on nearby tissues.
Ligands are signals that bind cell surface receptors (as observed with insulin (a ligand) and the insulin
receptor) or that can pass into the cell and bind an internal receptor (such as the steroid hormones).

4. 2. SIGNAL TRANSDUCTION
Any process occurring within cells that convert one kind of signal/stimulus into
another type.
It also known as cell signaling in which the transmission of molecular signals from
a cell's exterior to its interior.
Signals received by cells must be transmitted effectively into the cell to ensure an
appropriate response. This step is initiated by cell-surface receptors which triggers a
biochemical chain of events inside the cell, creating a response.

5. Messenger molecules may be amino acids, peptides, proteins,
fatty acids, lipids, nucleosides or nucleotides.

6. Different modes of cell communication

8. AUTOCRINE

9. ENDOCRINE
Signaling over long distance
Signal molecules(hormones) secreted by glands
Bloodstream carries hormones far and wide may
lie anywhere in the body

10. PARACRINE
Signaling molecules released by a secretory cell
affect only those target cells in close proximity. For
paracrine signals to act locally , secreted molecules
must not be allowed to diffuse to far.
• Rapidly taken up by neighboring target cells or
immobilized by ECM.
EXAMPLES:-
• conduction by a neurotransmitter of a signal
from one nerve cell to another or from a nerve cell
to a muscle cell
• Mostly studies neurotransmitters

11. RECEPTORS
 Receptors can be roughly divided into two major
classes: intracellular receptors and extracellular
receptors.
EXTRACELLULAR RECEPTORS
 Extracellular receptors are integral transmembrane proteins
and make up most receptors.
 They span the plasma membrane of the cell, with one part of
the receptor on the outside of the cell and the other on the inside.
 Signal transduction occurs as a result of a ligand binding to
the outside region of the receptor (the ligand does not pass
through the membrane).
Various Extracellular Receptors
 G protein-coupled receptors.
 Receptors with Kinase activity.
 Integrin receptors.
 Toll gate receptors.
 Ligand-gated ion channel receptors.

12. G-PROTEIN–COUPLED RECEPTORS (GPCRs)
 Also known as seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors, and G protein–
linked receptors (GPLR).
 These constitute a large protein family of receptors that sense molecules outside the cell and activate inside
signal transduction pathways and, ultimately, cellular responses.
Coupling with G proteins, they are called seven-transmembrane receptors because they pass through the cell
membrane seven times.
The ligands that bind and activate these receptors include:
light-sensitive compounds, odors, pheromones, hormones,
and neurotransmitters, and vary in size from small molecules
to peptides to large proteins.
G protein–coupled receptors are involved in many
diseases, and are also the target of approximately 40% of all
modern medicinal drugs.

14. RECEPTORS WITH KINASE ACTIVITY;
 A kinase is a type of enzyme that transfers phosphate groups
from high-energy donor molecules, such as ATP (see below) to
specific target molecules (substrates); the process is
termed phosphorylation.
 For every phosphorylation event, there is a phosphatase, an
enzyme that can remove phosphate residue and thus modulate
signaling
 Kinase enzymes that specifically phosphorylate tyrosine amino
acids are termed tyrosine kinases .
The signal binding domain of the receptor tyrosine
kinase is on the cell surface, while the tyrosine kinase
enzymatic activity resides in the cytoplasmic part of
the protein.

15. The most important groups of signals that bind to receptor tyrosine
kinases are:
peptide growth factors like nerve growth factor (NGF) and
epidermal growth factor (EGF)
peptide hormones, like insulin.
 Binding of signal molecules to the extracellular domains of
receptor tyrosine kinase molecules causes two receptor molecules to
dimerize .
 This brings the cytoplasmic tails of the receptors close to each
other and causes the tyrosine kinase activity of these tails to be
turned on.

16. The activated tails then phosphorylate each other on several tyrosine
residues. This is called autophosphorylation.
 The phosphorylation of tyrosines on the receptor tails triggers the
assembly of an intracellular signaling complex on the tails.
 The newly phosphorylated tyrosines serve as binding sites for a variety of
signaling proteins that then pass the message on to yet other proteins.
 An important protein that is subsequently activated by the signaling
complexes on the receptor tyrosine kinases is called RAS.

19. Diseases involving a decrease in the production of G proteins
include;
Night Blindness, where mutations in G(t) protein a subunits affect
the response of rod cells to light.
Pseudo hypoparathyroidism, where the genetic loss of G(s)
protein a subunits results in non-responsiveness to parathyroid
hormone.
Other abnormalities involve decreased signal initiation through
the inability of G proteins to switch to active states, e.g. the
symptoms of Whooping Cough (Pertussis) like hypoglycemia
Excessive G protein signaling can arise through either increased
signal initiation, or defective signal termination.
Increased signal initiation occurs in Testotoxicosis, where a
mutation in the receptor for luteinizing hormone can overstimulate
G(s) proteins, resulting in the excessive production of
testosterone.
Diseases arising from defective signal termination result from the
persistent elevated activity of downstream effectors, such as in
Cholera, the symptoms of which results from the action of a
bacterial toxin that lead to stimulation of adenylyl cyclase and the
subsequent secretion of salt and water leading to fatal diarrhea.Two other diseases involve defective termination through
mutations in G(s) protein a subunits, including;
Adenomas, in which G proteins lose their ability to hydrolyze GTP
through mutation, resulting in the excessive secretion of growth
hormone and the increased proliferation of somatotrophs.
McCune-Albright Syndrome, where scattered regions of skin
hyper-pigmentation arise from the hyper-functioning of one or
more endocrine glands.