1. Signal transmission and signal transduction
XIA Qiang, MD & PhD
Department of Physiology
Room 518, Block C, Research Building
School of Medicine, Zijingang Campus
Tel: ☆ (Undergraduate school),
(Medical school)

2. OUTLINE Intercellular signal transmission Signal transduction pathway
Chemical transmission
Electrical transmission
Signal transduction pathway
Pathways initiated by intracellular receptors
Pathways initiated by plasma membrane receptors

3. Intercellular signal transmission
Chemical transmission
Chemical signals
Neurotransmitters:

4. Intercellular signal transmission
Chemical transmission
Chemical signals
Neurotransmitters:
Humoral factors:
Hormones
Cytokines
Bioactivators

5. Intercellular signal transmission
Chemical transmission
Chemical signals
Neurotransmitters:
Humoral factors:
Gas: NO, CO, etc.

6. Intercellular signal transmission
Chemical transmission
Chemical signals
Receptors
Membrane receptors
Intracellular receptors

7. Receptors on the
surface of a cell
are typically
proteins that
span the membrane

8. Only Cell A has the
matching receptors
for this chemical
messenger, so it
is the only one
that responds
Cells B & C lack the matching receptors
Therefore are not directly affected by
the signal

11. Intercellular signal transmission
Electrical transmission
Gap junction

12. Cardiac Muscle
Low Magnification View
The intercalated disk is made of several types of intercellular junctions. The gap junction provides a low resistance pathway for the action potential to spread from cell to cell

13. Signal transduction pathway
Pathways initiated by intracellular receptors
Pathways initiated by plasma membrane receptors

14. This hydrophobic signal
requires a carrier protein
while in the plasma …
… but at the target cell
the signal moves easily
through the membrane
and binds to its receptor

15. Signal transduction pathway
Pathways initiated by intracellular receptors
Pathways initiated by plasma membrane receptors (transmembrane signal transduction)

16. Transmembrane signal transduction

17. Transmembrane signal transduction
Mediated by G protein-linked receptor
Mediated by enzyme-linked receptor
Mediated by ion channel

18. Binding of ligands to membrane-spanning receptors
activates diverse response mechanisms

19. Transmembrane signal transduction
Mediated by G protein-linked receptor
Mediated by enzyme-linked receptor
Mediated by ion channel

20. The Nobel Prize in Physiology or Medicine 1994
"G-proteins and the role of these proteins in signal transduction in cells"
Alfred G. Gilman
Martin Rodbell

21. The Discovery of G Proteins
Normal Lymphoma Cell
Mutated Lymphoma Cell

22. Activation and Inactivation of the G Protein
1. The G protein, composed of alpha-, beta- and gamma-subunits, in its resting state with bound GDP.
2. The receptor with bound hormone activates the G protein and replaces GDP...
3. ...with GTP and the G proteins is activated. The subunits separate.
4. Some seconds later the GTP, bound to the alpha-subunit, is hydrolysed to GDP. The subunits recombine.

23. G-protein-coupled Receptors

24.      Signaling molecules involved G protein effector
Second messenger
G protein effector
Protein kinase     

26. Main signaling pathways
(1) cAMP-PKA pathway (2) IP3-Ca2+ pathway (3) DG-PKC pathway (4) G protein-ion channel pathway

27. cAMP-PKA pathway
Gs, Gi

28. The cyclic AMP second messenger system

29. Adenylyl cyclase forms cAMP,
a “second messenger”
that activates enzymes
used in cellular responses
The phosphodiesterase
enzymes “terminate” the
second messenger cAMP

30. The cAMP system rapidly amplifies the response
capacity of cells: here, one “first messenger” led
to the formation of one million product molecules

31. Cells can respond via
the cAMP pathways
using a diversity
of cAMP-dependent
enzymes, channels,
organelles, contractile
filaments, ion pumps, and
changes in gene expression

32. (2) IP3-Ca2+ pathway: Gq (3) DG-PKC pathway: Gq
DAG: diacylglycerol
IP3: inositol 1,4,5-trisphosphate
PIP2: phospholipid phosphatidylinositol 4,5-bisphosphate

33. This receptor-G-protein complex is linked to and
activates phospholipase C, leading to an increase
in IP3 and DAG, which work together to activate
enzymes and to increase intracellular calcium levels

34. Membrane Bound Receptors,
Click here to play the
Membrane Bound Receptors,
G Proteins,
and Calcium Channels
Flash Animation

35. (4) G protein-ion channel pathway

36. Binding of the ligand to the receptor alters the receptor’s shape, which activates an associated G-protein, which then activates effector proteins,
i.e., enzyme functions or ion channels

39. The calcium-calmodulin
system is similar to some of
the cAMP pathways, because
it results in the activation of
protein kinases that can
phosphorylate key proteins
required for cellular responses

40. The “arachidonic acid cascade” is activated in inflammation responses; “cox inhibitors” block cyclooxygenase

41. Not all responses to
hydrophilic signals
are immediate:
Increases in gene expression
can occur, and the resulting
proteins can increase the
target cells’ response

42. Eicosanoid: A lipid mediator of inflammation derived from the 20-carbon atom arachidonic acid (20 in Greek is "eicosa") or a similar fatty acid. The eicosanoids include the prostaglandins, prostacyclin, thromboxane, and leukotrienes.

43. Transmembrane signal transduction
Mediated by G protein-linked receptor
Mediated by enzyme-linked receptor
Mediated by ion channel

44. Binding of the ligand to the receptor alters the receptor’s shape, which activates its enzyme function, phosphorylating an intracellular protein

45. (1) Tyrosine Kinase Receptor

46. Insulin receptor

47. Growth factor receptor

48. Mitogen-activated protein kinase (MAPK) pathway
PTK: protein tyrosine kinase
Ras: G protein. It consists of an a subunit, b subunit, and g subunit
MAPKKK: MAPK kinase kinase
MAPKK: MAPK kinase
MKP: MAPK phosphatases
TF: tissue factor

49. (2) Receptor-associated tyrosine kinase
JAK stands for Janus kinase or Just Another Kinase
JAK2=Tyrosine protein kinase 2

50. Binding of the ligand to the receptor alters the receptor’s shape, which activates an associated enzyme function, phosphorylating an intracellular protein

51. (3) Receptor guanylyl cyclase
Soluble GC

52. Transmembrane signal transduction
Mediated by G protein-linked receptor
Mediated by enzyme-linked receptor
Mediated by ion channel

53. Binding of the ligand to the receptor
alters the receptor’s shape, which
then opens (or closes) an ion channel

54. N2-ACh receptor channel

56. Any other pathway else? ? ?

57. Pheromone
Pheromones are chemicals emitted by living organisms to send messages to individuals of the same species.

58. The male silk moth bombyx mori (Fig
The male silk moth bombyx mori (Fig. 1, left) can detect very low quantities of the sex pheromone bombykol emitted by the female, and at the same time distinguishes bombykol from many other, often similar, volatile compounds in the air. A first step of olfaction is the tranfer of bombykol to the pheromone receptor at the neuronal membrane via the pheromone- binding protein (BmorPBP). Highly efficient uptake and release kinetics of bombykol at the pheromone binding protein is essential for olfactory function. However, BmorPBP features a central hydrophobic binding cavity for bombykol, completely encapsulating the ligand (Fig. 1, right) and the exit/entrance gate for bombykol is not known. Yet, the ligand has to enter and exit the cavity fast and reversibly.

59. THANK YOU FOR YOUR ATTENTION!