Biosignaling
Ye-Guang Chen
General introduction
Ion channels
G-protein coupled receptors
Second messengers
Tyrosine kinase receptors
From plasma membrane to the nucleus,
Regulation of gene expression
Cytokine signaling
Cell cycle
Apoptosis
Cell signaling and diseases
General introduction
Ion channels
G-protein coupled receptors
Second messengers
Tyrosine kinase receptors
From plasma membrane to the nucleus,
Regulation of gene expression
Cytokine signaling
Cell cycle
Apoptosis
Cell signaling and diseases
Four features of signal-
transducing systems.
General schemes of
intercellular signaling
Four general types of signal
transducers
General introduction
Ion channels
G-protein coupled receptors
Second messengers
Tyrosine kinase receptors
From plasma membrane to the nucleus,
Regulation of gene expression
Cytokine signaling
Cell cycle
Apoptosis
Cell signaling and diseases
Transmembrane
electrical potential
Role of voltage-gated and
ligand-gated ion channels in
neural transmission
Three states of the
acetylcholine receptor
General introduction
Ion channels
G-protein coupled receptors
Second messengers
Tyrosine kinase receptors
From plasma membrane to the nucleus,
Regulation of gene expression
Cytokine signaling
Cell cycle
Apoptosis
Cell signaling and diseases
Ligand-activated cell-surface receptors
?Ion-channel receptors,acetylcholine
?G-protein-coupled receptors,epinephrine,
glucagon,serotonin
?Tyrosine kinase-linked receptors,EGF,PDGF,
interferons,insulin
?Tyrosine phosphatase receptors,CD45
?Serine/therinine kinase receptors,TGFb,BMP
?Guanylate cyclase receptor,atrial naturetic factor
Epineph
rine
Produced by Chromaffin cells in adrenal medulla
Functions,
Increase heart rate,blood pressure,
sweating,rate of respiration
Stimulate conversion of glycogen to glucose
Transduction of the
epinephrine signal,the b-
adrenergic pathway
Self-inactivation of Gs
The Nobel Prize in Physiology or
Medicine 1994
“for their discoveries of G-proteins and the role of these
proteins in signal transduction in cells”
Interaction of Gsa with adenylyl
cyclase
GTP
Adenylyl
cyclase Forskolin
Gsa
Activation of cAMP-
dependent protein kinase
(PKA)
dephosphorylation cycle
of proteins
The Nobel Prize in Physiology or
Medicine 1992
“for their discoveries concerning reversible protein
phosphorylation as a biological regulatory mechanism”
Adenosine 5’-
monophosphate
Inactivation
of cAMP
Epinephrine cascade,A
example of signal
amplification
that cause cholera (affecting
Gsa) and whooping cough
(pertussis) (affecting Gia)
Movie,G
protein
Q u ic kT i m e? a n d a
A n im a t i o n d e c o m p re s s o r
a re n e e d e d t o s e e t h i s p ic t u re,
Desensitization of the b-
adrenergic receptor
General introduction
Ion channels
G-protein coupled receptors
Second messengers
Tyrosine kinase receptors
From plasma membrane to the nucleus,
Regulation of gene expression
Cytokine signaling
Cell cycle
Apoptosis
Cell signaling and diseases
cAMP
cGMP
Inosite1,4,5-triphosphate (IP3)
Diacylglycerol
Ca2+
Intracellular Second
Messengers
Hormon
e-
activated
pospholi
pase C
and IP 3
Movie,Second
messengers
Q u ic kT i m e? a n d a
A n im a t i o n d e c o m p re s s o r
a re n e e d e d t o s e e t h i s p ic t u re,
Triggering of oscillations in
intracellular [Ca2+] by
extracelluar signals
General introduction
Ion channels
G-protein coupled receptors
Second messengers
Tyrosine kinase receptors
From plasma membrane to the nucleus,
Regulation of gene expression
Cytokine signaling
Cell cycle
Apoptosis
Cell signaling and diseases
Structure and activation of
receptor tyrosine kinases
Insulin receptor
Regulation of gene expression
by insulin
Activation of glycogen
synthesis by insulin
Regulation of blood
glucose level
GTP-binding proteins,A
superfamily
?Trimeric G proteins,Gs,Gi,Gq
?Small GTP-binding proteins
?Ras,cell growth
?Rac,Rho,Cdc42,cell migration
?Rab:membrane trafficking
?ARF,membrane trafficking
?Ran,Nuclear transport
?Other GTP-binding proteins,Dynamin
GTP-GDP cycling of
Ras protein
GTP-GDP cycling of
Ras protein
Common features of signaling
systems that detect
hormones,light,smells and tastes
General introduction
Ion channels
G-protein coupled receptors
Second messengers
Tyrosine kinase receptors
Regulation of gene expression,From
plasma membrane to the nucleus
Cytokine signaling
Cell cycle
Apoptosis
Cell signaling and diseases
General introduction
Ion channels
G-protein coupled receptors
Second messengers
Tyrosine kinase receptors
From plasma membrane to the nucleus,
Regulation of gene expression
Cytokine signaling
Cell cycle
Apoptosis
Cell signaling and diseases
Cytokine
signaling
Movie,TGFb
signaling
Q u ic kT i m e? a n d a
A n im a t i o n d e c o m p re s s o r
a re n e e d e d t o s e e t h i s p ic t u re,
retinoids,vitamin D and
thyroid hormones
Ye-Guang Chen
General introduction
Ion channels
G-protein coupled receptors
Second messengers
Tyrosine kinase receptors
From plasma membrane to the nucleus,
Regulation of gene expression
Cytokine signaling
Cell cycle
Apoptosis
Cell signaling and diseases
General introduction
Ion channels
G-protein coupled receptors
Second messengers
Tyrosine kinase receptors
From plasma membrane to the nucleus,
Regulation of gene expression
Cytokine signaling
Cell cycle
Apoptosis
Cell signaling and diseases
Four features of signal-
transducing systems.
General schemes of
intercellular signaling
Four general types of signal
transducers
General introduction
Ion channels
G-protein coupled receptors
Second messengers
Tyrosine kinase receptors
From plasma membrane to the nucleus,
Regulation of gene expression
Cytokine signaling
Cell cycle
Apoptosis
Cell signaling and diseases
Transmembrane
electrical potential
Role of voltage-gated and
ligand-gated ion channels in
neural transmission
Three states of the
acetylcholine receptor
General introduction
Ion channels
G-protein coupled receptors
Second messengers
Tyrosine kinase receptors
From plasma membrane to the nucleus,
Regulation of gene expression
Cytokine signaling
Cell cycle
Apoptosis
Cell signaling and diseases
Ligand-activated cell-surface receptors
?Ion-channel receptors,acetylcholine
?G-protein-coupled receptors,epinephrine,
glucagon,serotonin
?Tyrosine kinase-linked receptors,EGF,PDGF,
interferons,insulin
?Tyrosine phosphatase receptors,CD45
?Serine/therinine kinase receptors,TGFb,BMP
?Guanylate cyclase receptor,atrial naturetic factor
Epineph
rine
Produced by Chromaffin cells in adrenal medulla
Functions,
Increase heart rate,blood pressure,
sweating,rate of respiration
Stimulate conversion of glycogen to glucose
Transduction of the
epinephrine signal,the b-
adrenergic pathway
Self-inactivation of Gs
The Nobel Prize in Physiology or
Medicine 1994
“for their discoveries of G-proteins and the role of these
proteins in signal transduction in cells”
Interaction of Gsa with adenylyl
cyclase
GTP
Adenylyl
cyclase Forskolin
Gsa
Activation of cAMP-
dependent protein kinase
(PKA)
dephosphorylation cycle
of proteins
The Nobel Prize in Physiology or
Medicine 1992
“for their discoveries concerning reversible protein
phosphorylation as a biological regulatory mechanism”
Adenosine 5’-
monophosphate
Inactivation
of cAMP
Epinephrine cascade,A
example of signal
amplification
that cause cholera (affecting
Gsa) and whooping cough
(pertussis) (affecting Gia)
Movie,G
protein
Q u ic kT i m e? a n d a
A n im a t i o n d e c o m p re s s o r
a re n e e d e d t o s e e t h i s p ic t u re,
Desensitization of the b-
adrenergic receptor
General introduction
Ion channels
G-protein coupled receptors
Second messengers
Tyrosine kinase receptors
From plasma membrane to the nucleus,
Regulation of gene expression
Cytokine signaling
Cell cycle
Apoptosis
Cell signaling and diseases
cAMP
cGMP
Inosite1,4,5-triphosphate (IP3)
Diacylglycerol
Ca2+
Intracellular Second
Messengers
Hormon
e-
activated
pospholi
pase C
and IP 3
Movie,Second
messengers
Q u ic kT i m e? a n d a
A n im a t i o n d e c o m p re s s o r
a re n e e d e d t o s e e t h i s p ic t u re,
Triggering of oscillations in
intracellular [Ca2+] by
extracelluar signals
General introduction
Ion channels
G-protein coupled receptors
Second messengers
Tyrosine kinase receptors
From plasma membrane to the nucleus,
Regulation of gene expression
Cytokine signaling
Cell cycle
Apoptosis
Cell signaling and diseases
Structure and activation of
receptor tyrosine kinases
Insulin receptor
Regulation of gene expression
by insulin
Activation of glycogen
synthesis by insulin
Regulation of blood
glucose level
GTP-binding proteins,A
superfamily
?Trimeric G proteins,Gs,Gi,Gq
?Small GTP-binding proteins
?Ras,cell growth
?Rac,Rho,Cdc42,cell migration
?Rab:membrane trafficking
?ARF,membrane trafficking
?Ran,Nuclear transport
?Other GTP-binding proteins,Dynamin
GTP-GDP cycling of
Ras protein
GTP-GDP cycling of
Ras protein
Common features of signaling
systems that detect
hormones,light,smells and tastes
General introduction
Ion channels
G-protein coupled receptors
Second messengers
Tyrosine kinase receptors
Regulation of gene expression,From
plasma membrane to the nucleus
Cytokine signaling
Cell cycle
Apoptosis
Cell signaling and diseases
General introduction
Ion channels
G-protein coupled receptors
Second messengers
Tyrosine kinase receptors
From plasma membrane to the nucleus,
Regulation of gene expression
Cytokine signaling
Cell cycle
Apoptosis
Cell signaling and diseases
Cytokine
signaling
Movie,TGFb
signaling
Q u ic kT i m e? a n d a
A n im a t i o n d e c o m p re s s o r
a re n e e d e d t o s e e t h i s p ic t u re,
retinoids,vitamin D and
thyroid hormones
