Download Kinase Phosphatase Kinase Phosphatase O P O O P O OH OH Tyr

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External environment
Cytoplasm
Signal
transduction
pathway
Cellular
response
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Direct Contact
Paracrine Signaling
Endocrine Signaling
Adjacent
plasma
membrane
Membrane receptor
Signal
transduction
pathway
Hydrophilic
ligand
Synaptic Signaling
Hormone secretion into
blood by endocrine gland
Secretory cell
Cellular
response
Nerve cell
Neurotransmitter
Blood vessel
Plasma
membrane
Adjacent
target cells
Synaptic gap
Distant target cells
Target cell
a.
Intracellular receptor
Hydrophobic
ligand
b.
c.
d.
Plasma membrane
1
2
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Ligand (signal)
Ions
ATP
Ser
or
Thr
ADP
Ser
or
Thr
Kinase
OH
O
O
Phosphatase
P
Ligand
(signal)
O–
Inactive
O–
Pi
Active
Cellular
response
Ions
a.
b.
Ligand
(signal)
Ions
GPCR
ATP
Tyr
O
ADP
Kinase
OH
Tyr
O
P
O–
γ
α
γ
β
O–
Phosphatase
G protein
Pi
β
Ion channel
Enzyme
G protein activates
GTP
either enzyme or ion channel
GDP
α
α
GTP
c.
3
4
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Ligands
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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
DNA-binding
site exposed
5. Cellular
response is
a change in
gene
expression.
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.
Transmembrane RTK proteins
P
P
P
P
Phosphate
groups
P
P
P
P
P
P
P
P
P
P
P
P
P
Dimerization and
autophosphorylation
Cellular
response
P
Phosphorylated protein
Intracellular kinase domain
Extracellular ligand-binding domain
1. Ligand binds to the receptor.
5
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
ATP
Signal amplification
cAMP + PPi
cAMP
O
Receptor
–O
Receptor
MKKK
MKKK
O
O
P
–O
O
O
P
O
CH2
O
N
CH2
Adenylyl cyclase
–O
MKK
MKK
Active
Inactive
MK
P
Second
kinase
P
O
–O
O
PP i
O
P
–O
MKKK
MKKK
MKK
MKK
MKK
O
P
O–
O–
O–
Extracellular space
MKKK
MKKK
MKKK
MKKK
N
O
O
O
a.
Ras
First
kinase
P
–O
Activator
Activator
NH2
NH2
Signal
Signal
MK
Plasma
membrane
Response proteins
P
Active
Inactive
O
P
MAP
kinase
MK
P
MKK
MKK
MKK
MK
P
MK
MK
Cellular responses
P
Active
Inactive
Response
proteins
Response
Response
proteins
proteins
Response
Cellular
response
O
C
C
O
O
C
C
O
O–
C
O
O
b.
–O
P
O
O
P
Cytoplasm
O
C
O
O
C
C
O–
Cleaved by
phospholipase C
DAG
O–
Phospholipase C
O–
O
O
P O–
P
O
O
O
O
P
O
C
OH
O
OH
OH OH
C
O–
O–
IP3
OH
OH OH
O
O
P
O–
O–
PIP2
a.
DAG + IP3
b.
7
8
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Ligand
Ligand
Phospholipase C
GPCR
Adenylyl cyclase
GPCR
β γ
α
β
β
γ
γ
GTP
PIP
DAG
GTP
GDP
α
GDP
β γ
cAMP
IP3
ATP
Cytoplasm
Cytoplasm
Ca2+
binding
protein
Activates PKA
ER
Response
protein
Cellular
response
Nucleus
Ca2+
Cellular
response
9
10
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Ca2+
Ca2+
Epinephrine
Adenylyl
GPCR
cyclase
Ca2+
Adenylyl
cyclase
Glucagon
Inactive
protein
GTP
GD P
GTP
ATP
ATP
cAM P
Calmodulin
PK A
GD P
Cytoplasm
P
P
P
P
P
P
P
P
Calmodulin
Ca2+
Glycogen
phosphorylase
Active
protein
Ca2+
a.
Phosphorylase
kinase
P
CH2
b.
Glycogen
11
Glucose-6-phosphate
12