Download Cytoplasm External environment Membrane receptor Intracellular

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External environment
Cytoplasm
Signal
transduction
pathway
Cellular
response
Membrane receptor
Signal
transduction
pathway
Hydrophilic
ligand
Cellular
response
Intracellular receptor
Hydrophobic
ligand
Plasma membrane
1
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Direct Contact
Paracrine Signaling
Secretory cell
Endocrine Signaling
Hormone secretion into
blood by endocrine gland
Synaptic Signaling
Nerve cell
Neurotransmitter
Adjacent
plasma
membrane
Blood vessel
Plasma
membrane
Adjacent
target cells
Synaptic gap
Distant target cells
Target cell
a.
b.
c.
d.
2
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Ser
or
Thr
ATP
ADP
Kinase
OH
Ser
or
Thr
O
O
P
O–
O–
Phosphatase
Pi
ATP
Tyr
Kinase
OH
O
ADP
Phosphatase
Tyr
O
P
O–
O–
Pi
3
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Ligand (signal)
Ions
Ligand
(signal)
Inactive
Active
Cellular
response
Ions
a.
b.
Ligand
(signal)
Ions
GPCR
b
G protein
g
a
b
Ion channel
GDP
g
a
Enzyme
G protein activates
GTP
either enzyme or ion channel
a
GTP
c.
4
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2. Hormone binding
alters receptor
conformation so it no
longer binds inhibitor.
Hormone
Signal moleculebinding domain
1. Hormones cross
plasma membrane
and bind to
cytoplasmic
receptors.
Inhibitor
5. Cellular
response is
a change in
gene
expression.
DNA-binding
site exposed
Inhibitor
Transcription-activating domain
DNA-binding
site blocked
3. Hormone–receptor
complex translocates
to nucleus.
Gene
transcription
4. Hormone–receptor
complex binds to DNA.
This usually turns on
transcription, but can
also turn it off.
5
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Ligands
P
P
P
P
P
P
P
P
P
P
P
P
P
P
P
P
Phosphate
groups
Dimerization and
autophosphorylation
Transmembrane RTK proteins
P
Cellular
response
P
Phosphorylated protein
Intracellular kinase domain
Extracellular ligand-binding domain
1. Ligand binds to the receptor.
2. Two receptors associate (dimerize)
and phosphorylate each other
(autophosphorylation).
3. Response proteins bind to phosphotyrosine on receptor. Receptor can
phosphorylate other response proteins.
6
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MAP kinase cascade
Signal amplification
Signal
Signal
Receptor
Receptor
Activator
MKKK
MKKK
Activator
MKKK
MKKK
Ras
MKK
MKK
First
kinase
MKKK
MKKK
Active
Inactive
MK
P
Second
kinase
MKK
MKK
MKK
MKK
MK
MK
MK
P
Response proteins
P
Active
Inactive
P
MAP
kinase
MKK
MKK
MKKK
MKKK
MK
Inactive
P
MK
Cellular responses
P
Active
b.
Response
proteins
Response
Response
proteins
proteins
Response
Cellular
response
a.
7
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ATP
cAMP + PPi
NH2
NH2
cAMP
O
–O
P
–O
O
O
P
–O
O
O
P
O
CH2
O
N
CH2
Adenylyl cyclase
–O
N
O
O
O
O
P
–O
O
P
–O
PP i
O
O
O–
P
O–
O–
a.
Extracellular space
Plasma
membrane
O
C
C
O
O
C
C
O
O–
C
O
–O
O
P
O
O
P
Cytoplasm
C
C
O
O
C
C
O–
Cleaved by
phospholipase C
O
OH
OH OH
O–
Phospholipase C
O–
O–
O
O
P O–
P
O
O
O
O
P
DAG
C
OH
O
O
O
O–
IP3
OH
OH OH
O
O
P
O–
O–
PIP2
b.
DAG + IP3
8
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Ligand
Adenylyl cyclase
GPCR
b
g
b
g
a
GDP
GTP
cAMP
ATP
Cytoplasm
Activates PKA
Response
protein
Nucleus
Cellular
response
9
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Ligand
Phospholipase C
GPCR
b g
a
GDP
b g
PIP
DAG
GTP
IP3
Cytoplasm
Ca2+
binding
protein
ER
Ca2+
Cellular
response
10
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Ca2+
Ca2+
Ca2+
Inactive
protein
Calmodulin
Calmodulin
Ca2+
Active
protein
Ca2+
a.
b.
11
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Epinephrine
Adenylyl
GPCR
cyclase
Adenylyl
cyclase
Glucagon
GTP
GTP
ATP
ATP
cAM P
PKA
Cytoplasm
P
P
P
P
Phosphorylase
kinase
P
P
P
P
Glycogen
phosphorylase
P
CH2
Glycogen
Glucose-6-phosphate
12