4. • Signaling molecules, which are
released by signal-producing cells,
reach and transfer biological signals
to their target cells to initiate specific
cellular responses.
5. protein & peptides: Hormone, cytokine
AA & its derivatives:
Gly, Glu, adrenaline, thyro
xine
Steroid: Sex Hormone,
glucocorticosteroid
Fatty acid derivatives: prostaglandin
6. • Secreted by common cells.
• Reach neighboring target cells by
passive diffusion.
• Time of action is short.
• Such as GF, PG
7. • Secreted by endocrine cells.
• Reach target cells by blood circulation.
• Time of action is long.
• Such as insulin, thyroxine, adrenalin
8. • Secreted by neuronal cells.
• Reach another neuron by synaptic
gap.
• Time of action is short.
• Such as Acetylcholine
(Ach), noradrenaline
9. • Simple structure, half life is short
and active in chemistry .
• Such as NO, CO.
10. • Act back to their own cells.
• Such as GF, cytokine, interferon,
interleukin.
13. Small molecules synthesized in cells
in response to an external signal are the
second messengers, which are
responsible for intracellular signal
transduction.
Such as
Ca2+, DG, Cer, IP3, cAMP, cGMP
14. Third messengers are the molecules
which transmit message from outside to
inside of nucleous or from inside to
outside of nucleous, also called DNA
binding protein.
15. Receptors are specific membrane
proteins, which are able to recognize and
bind to corresponding ligand
molecules, become activated, and
transduce signal to next signaling
molecules.
Glycoprotein or Lipoprotein
16. ligand
A small molecule that binds
specifically to a larger one; for
example, a hormone is the ligand for
its specific protein receptor.
17. (1) Ligand-gate ion channels type
(cyclic receptor)
ligand→receptor→ion channel open or
close
22. • G protein refers to any protein which
binds to GDP or GTP and act as signal
transduction.
• G proteins consist of three different
subunits (, , -subunit).
• -subunit carries GTPase activity,
binding and hydrolysis of GTP.
23. G protein Coupled Receptors
• The human genome encodes more than 1000
Gprotein
Coupled Receptors (GPCR), that transduce
messages as diverse as light, smells, taste, and
hormones
• An example is the beta-adrenergic receptor, that
mediates the effects of epinephrine on many
tissues:…
30. Gs vs Gi vs Gq
Gs and Gi coupled to adenylate cyclase [cAMP]
G q coupled to phospholipase C [Ca2+]
31. Gs vs. Gi
Regulation of Adenylate Cyclase Activity
Gs stimulates adenylate cyclase
Gi inhibits adenylate cyclase
e.g. epinephrine can increase or decrease intracellular cAMP concentrations,
depending upon the receptor to which it binds
adrenergic receptors couple to Gs, whereas
2 adrenergic receptors couple to Gi
39. Intracellular R is trans-acting
element cis-acting element
gene expression
Localized in the cytosol and/or in the
nucleus.
ligand: Steroid H, Vit D3, Thyroxine
51. hormons: glucagon, epinephrine
inactive ACactive AC
ATP cAMP
inactive PKA active PKA
phosphorylase b kinase
phosphorylase b kinase
P
ATP
ADP
H2O
Pi
phosphorylase b
P
P
ATP ADP
Pi
H2O
ATP ADP
glycogen
synthase
glycogen
synthase
P
H2OPi
protein
phosphatase-1
(active) (inactive)
inhibitor-1
(active)
inhibitor-1
(inactive)
phosphorylase a
ATP
52.
53. (1) Ca2+ -DAG -dependent PKC pathway
H R
PIP2
G protein PLC
IP3 DG
ER
PKC
Ca2+
Biological effects
Phosphorylation of Es or functional proteins
54.
55. IP3 + R→open of Ca2＋
channel →[Ca2＋]↑ from ER
[Ca 2+]i 0.01-1 mol/L（10-7 mol/L ）
[Ca 2+]o 2.5mmol/L（10-3 mol/L ）
5000~10000×
Ca2＋
DG PKC ↑
56.
57. • regulation of metabolism
PKC →Ser/Thr-P of R, enzyme,
Protein of Mb.
• Gene expression
58.
59. H R G protein PLC
IP3
Ca2+ CaM
CaMK
Biological effects
Phosphorylation of Es or functional proteins
60. Ca2＋ binding protein
4 Ca2＋+ CaM → Ca2＋- CaM
↓
CaM kinase↑
↓
Ser/Thr - P
↓
Ca2＋ pump, AC ↑ GC ↑
Es (glycogen synthase, phosphorylase
kinase)
66. • TPK receptor is related to
proliferation, differentiation,
dissociation, carcinomatous
change.
• TPK：
receptor TPK：Membrane.
non receptor TPK：cytosol
67. • GRB2, SOS, Ras, Raf
• Small G protein: Ras
• MAPK (mitogen-activated protein kinase)：
MAPK、MAPKK、MAPKKK
• MAPKs belong to a family of serine/threonine kinases
(kinases add
phosphate groups to/phosphorylate other proteins)
• They participate in cell
growth, differentiation, transformation,
apoptosis (controlled cell death) and others
