This document provides an overview of signal transduction. It begins with defining signal transduction as the process by which extracellular signaling molecules activate cell surface or intracellular receptors, triggering a biochemical chain reaction that results in a cellular response. The document then discusses the history of studying signal transduction, examples of environmental stimuli, types of receptors, second messengers, cellular responses, and major signaling pathways involved in signal transduction like the MAPK/ERK, cAMP-dependent, and IP3/DAG pathways.

1. SIGNAL
TRANSDUCTION
Muhammad Umer Zafar (2191)
Turan Kaya (2148)
Paul Adeyemo (2193)

2. STRUCTURE
 What is signal transduction? (Turan)
 History (Turan)
 Environmental stimuli (Turan)
 Receptors (Muhammad Umer)
- Extracellular
- Intracellular
 Cellular responses (Paul)
 Major pathways (Paul)

3. WHAT IS SIGNAL TRANSDUCTION?
 Signal transduction occurs when an extracellular
signaling molecule activates a specific receptor located on
the cell surface or inside the cell. In turn, this receptor
triggers a biochemical chain of events inside the cell,
eventually eliciting a response.
 Depending on the cell, the response may alter the
cell's metabolism
-shape
-gene expression
-ability to divide.
 The signal can be amplified at any -step. Thus, one
signalling molecule can generate a response involving
hundreds to millions of molecules.

5. HISTORY
 In 1970, Martin Rodbell examined the effects
of glucagon on a rat's liver cell membrane receptor. He
noted that guanosine triphosphate disassociated
glucagon from this receptor and stimulated the G-
protein, which strongly influenced the cell's metabolism.
Thus, he deduced that the G-protein is a transducer that
accepts glucagon molecules and affects the cell.
 For this, he shared the 1994 Nobel Prize in Physiology
or Medicine with Alfred G. Gilman.

6. ENVIRONMENTAL STIMULI
Examples include
 photons hitting cells in the retina of the eye,
and odorants binding to odorant receptors in the nasal
epithelium.
 In microbial molecules, viral nucleotides and
protein antigens, can elicit an immune system response
against invading pathogens mediated by signal transduction
processes, i.e. plant-pathogen resistance in Arabidopsis
thaliana.
 In Unicellular, slime molds secrete cyclic adenosine
monophosphate upon starvation, stimulating individual cells
in the immediate environment to aggregate yeast cells used
for mating factors

7. RECEPTORS
 Extracellular
-G protein coupled receptor
-Tyrosine and histidine kinase
-Integrin
-Toll gate
-Ligand-gated ion channel
 Intracellular
-Nuclear receptors
-Cytoplasmic receptors
 Second messengers
-Calcium
-Lipophilics
-Nitric oxide
-Redox signalling

8. SIMPLE RECEPTOR ACTIVATION

9. 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
 Types
-G protein coupled receptor
-Tyrosine and histidine kinase
-Integrin
-Toll gate
-Ligand-gated ion channel

10. G PROTEIN COUPLED RECEPTOR
 Family of integral
transmembrane proteins
that possess seven
transmembrane domains
and are linked to a
heterotrimeric G protein.
 Adrenergic
receptors and chemokine
receptors.

11. TYROSINE AND HISTIDINE KINASE
 Transmembrane proteins with an
intracellular kinase domain and an extracellular
domain that binds ligands;
 Growth factor receptors such as the insulin receptor

12. INTEGRIN
 Attachment to other cells and the extracellular
matrix and in the transduction of signals from
extracellular matrix components such
as fibronectin and collagen.

13. TOLL GATE
 Toll-like receptors (TLRs) are a class of proteins that
play a key role in the innate immune system.

14. LIGAND-GATED 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
(i.e. a ligand), such as a neurotransmitter.

15. INTRACELLULAR
 Nuclear receptors
The typical ligands for nuclear receptors are non-polar
hormones like
the steroid hormones testosterone and progesterone
and derivatives of vitamins A and D
 Cytoplasmic receptors
 NOD-like receptors (NLRs)
 Leucine-rich repeat (LRR) motif similar to TLRs.
 Cytokines such as interleukin-1β.

16. SECOND MESSENGERS
 First messengers are signalling molecules (hormones)
 Second messengers are that act within the cell such
as:-
 Calcium (Ca ions transportation)
 Lipophilics (derived from lipids diacylglycerol,
ceramide,and protein kinase C.)
 Nitric oxide (free radical-apoptosis & penile erections)
 Redox signalling (CO, H2O2, H2S, superoxide)

17. CELLULAR RESPONSES
 Gene activations and metabolism alterations are
examples of cellular responses. 3 basic signals are:
 Stimulatory (growth factors)
 Posttranslational_modification (PMT)
 Transcription independent response
i.e. epidermal growth factor (EGF) binds
the epidermal growth factor receptor (EGFR),
which causes dimerization and
autophosphorylation of the EGFR, which in turn
activates the intracellular signaling pathway
 Inhibitory (cell-cell contact)
 Permissive (cell-matrix interactions)

18. MAJOR PATHWAYS
 MAPK/ERK pathway: pathway that couples
intracellular responses to growth
factors on cell surface receptors. It is very complex
and includes many protein components promotes cell
division, & cancer are associated with aberrations in it.

19. MAJOR PATHWAYS
 cAMP-dependent pathway: In humans, cAMP works
by activating protein kinase A (PKA, cAMP-dependent
and further effects depend mainly on cAMP, which
vary based on the type of cell.

20. MAJOR PATHWAYS
 IP3/DAG pathway: PLC cleaves
the phospholipid phosphatidylinositol 4,5-
bisphosphate (PIP2) yielding diacyl glycerol (DAG)
and inositol 1,4,5-triphosphate (IP3). DAG remains bound
to the membrane, and IP3 is released as a soluble structure
into the cytosol. IP3 then diffuses through the cytosol to
bind to IP3 receptors, particular calcium channels in
the endoplasmic reticulum (ER). These channels are
specific to calcium and allow the passage of only calcium to
move through. This causes the cytosolic concentration of
Calcium to increase, causing a cascade of intracellular
changes and activity. In addition, calcium and DAG
together works to activate PKC, which goes on to
phosphorylate other molecules, leading to altered cellular
activity. End-effects include taste, manic depression, tumor
promotion, etc.