This is a Powerpoint made by a myself for the PG seminar in front of Professors. For the preparation standard books were followed and guidance from expertise was taken. This will be helpful for UG and PG students of Medical and life science students.

1. Signal Transduction
Surendra Marasini
M.Sc. Medical Biochemistry
B.P. Koirala Institute of Health
Sciences, Dharan, Nepal

2. Overviews
• Introduction
• Metabolism Vs. cell signaling
• Characteristic features of signal transduction
• Signal transduction via different mechanisms
• Receptors

3. Introduction
The cell senses extracellular signals
• Hormones, pheromones, heat, light, osmotic pressure,
concentration change of glucose, Na+, K+ etc
And commutes them into intracellular signals
• Involves same types of molecular modification as that
of metabolism
• Production and degradation of substances, activation or
inhibition of reactions

4. What is the difference then ??
Metabolism Signaltransduction
Provides mass transfer Provides information transfer
Quantity of converted material µM
or mM
10 to 104 molecules/cell
A metabolic network is determined
by present set of enzymes
A signal pathway may assemble
dynamically

5. How cells communicate signals??

6. Characteristic features of signal
transduction

9. Receptor ligand interaction can be
quantified
• Scatchard analysis quantifies the receptor
ligand interaction
• Hormone/ligand (L) binds with receptor R
specifically and tightly

10. ………(1)
………(2)
………(3)
………(4)

11. Fig: Scatchard analysis & plots .

12. Receptor types
1. G protein coupled receptor
2. Receptor tyrosine kinase
3. Receptor guanylyl cyclases
4. Gated ion channels
5. Adhesion receptors
6. Nuclear receptors

13. General types of signal transductions

14. G protein coupled receptor
• Member of a guanosine nucleotide binding protein
• Three essential components define GPCR (plasma
membrane receptor, G protein and effector enzyme or
ion channel in the plasma membrane )
• The human genome encodes about 350 GPCRs for
detecting hormones, growth factors and other
endogenous ligands

19. Activation of CAMP dependent protein
kinase

20. Role of phosphodiesterase
• Hydrolytic enzyme ensures the turnovers of
the signal (cAMP).
• > 11 members of phosphodiesterase
• Inhibitors of phosphodiesterase- methylated
xanthine derivatives – increase cAMP level

21. Diacylglycerol, inositol triphosphate and
calcium have related roles in second
messengers
• Phosphatidylinositol 4,5 bisphate
Phospholipase C
Inositol triphosphate + 1,2 Diacyl glycerol

23. Some signals that act through PLc, IP3 &
Ca++
Source: Lehninger′s Biochemistry

24. Calmodulin
• Most important Ca2+
binding protein
• Binds four Ca2+ in a
cooperative manner
• Stimulus- increase
intracellular Ca2+-
Calcium calmodulin
complex-change in
conformation-activates
CaM kinase-
Phosphorylation of target
proteins

26. 2.Receptor tyrosine Kinase
• α subunit –extracellular
• β subunit-
transmembrane
• Autophosphorylation of
beta subunits
• Receptor tyrosine kinase
also phosphorylates the
insulin receptors

27. Fig: receptor tyrosine kinase having different growth factor receptors

28. JAK STAT signaling system also involves
Tyrosine Kinase activity
• No intrinsic protein kinase activity but when
occupied by their ligand, bind a cytosolic
tyrosine kinase
• For example: system that regulates the
formation of erythrocytes in mammals
• Cytokines and erythropoietin

29. JAK STAT transduction contd…
• Dimerized receptor
activates Janus Kinase (
JAK),
• Activated JAK
phosphorylates several
Tyr residues in
cytoplasmic domain
• SH2 domain in STAT5
binds p-Tyr residues
• Nucleus : expression of
gene

30. 3. Cyclic GMP and Receptor guanylyl
cyclase & protein kinase G
• Guanylyl cyclase when activated convert
GTP to second messenger cyclic Guanosine
5′3′ monophosphate (cGMP)

31. Fig:Two types of guanylyl cyclase that participate in signal transduction

32. Factors that increase cGMP
• Nitric oxide
• Nitroglycerin
• Nitroprusside
• Na nitrite
• Na azide
(potent vasodilators)

33. 4.Gated ion channels
• Certain cells in multicellular organism are
excitable
• Play central role in nerve conduction, muscle
contraction, hormone secretion, sensory processes
and learning and memory.
• Excitability of these cells depends on ion
channels
• Signal transducers provide a regulated path for
movement of inorganic ions Na+, K+, Ca++ and Cl-

34. Fig : Transmembrane Electrical potential

35. Voltage gated ion channels produce
neuronal action potentials
• Signaling in the nervous system is
accomplished by network of neurons which
carry electrical impulse from cell body through
axons.
• The electrical signals triggers the release of
neurotransmitter molecules at the synapse
carrying the signal to the next cell.
• Three types of voltage gated ion channels
(Na+, K+ and Ca++)

36. Fig: Role of voltage gated and
Ligand gated ion channels
In nerve impulse transmission

37. 5.Adhesion receptors/Integrins
• Proteins of plasma membrane that mediates the
adhesion of cells to each other and to the
extracellular matrix
• Carry signals in both directions across the
membrane
• 24 different integrins found having unique
functions
• Extracellular ligands interact with integrins are
collagen, fibrinogen, fibronectin & many other
types recognized by integrins : -Arg-Gly-Asp
(RGD)

38. Fig: Two way signalling by integrins

39. Regulation of Transcription by nuclear
Hormone receptors
• Steroid, retinoid and thyroid hormone exert
effect by these mechanisms.
• Act in the nucleus to alter gene expression
• Steroid hormones (Estrogen, Progesterone
and cortisol )- hydrophobic-transported in a
specific carrier proteins to the target tissue
• In target cells, these are absorbed by simple
diffusion and bind to specific receptors in the
nucleus

40. Fig: general mechanism by which steroid and thyroid hormones act

41. Hormone action & signal transduction
Source: Harper′s Illustrated Biochemistry

42. Ligand receptor complex is the trigger
for Group I hormones
Fig: regulation of gene expression by Thyroid and Glucocorticoid hormones
glucocoricoid
Thyroid &retinoid

43. Fig: DNA sequences of several hormone response elements

44. Disorders of the signal transduction
• Cancer and other diseases
• Eg CML
• Cholera and whopping cough
( altered G protein activity)

45. References
1. Lehninger′s Biochemistry 6th Edition
2. Harper′s Illustrated Biochemistry 30th Edition